What Is Fibroblast Growth Factor 23? Definition and What Research Reports
Fibroblast growth factor 23 (FGF23) is a bone-derived peptide hormone that signals to the kidney and other tissues to regulate phosphate and vitamin D handling. It is an endogenous protein studied as a biomarker rather than an injectable research peptide. Published work has examined FGF23 in chronic kidney disease, kidney transplantation, acute myocardial infarction, cartilage cell differentiation, intestinal magnesium handling, iron and erythropoietin signalling, and COVID-19, and has mapped its protein in rat brain tissue.
Definition
Fibroblast growth factor 23 (FGF23) is a peptide hormone produced chiefly by bone cells — osteocytes and osteoblasts — that circulates in blood and acts on distant tissues, most notably the kidney, to regulate phosphate excretion and vitamin D metabolism. It belongs to the fibroblast growth factor superfamily, and specifically to the “endocrine” FGF19 subfamily, whose members travel through the bloodstream rather than acting only on neighbouring cells. Unlike classical FGFs, FGF23 binds poorly to heparan sulfate and instead requires the co-receptor α-Klotho to activate FGF receptors with high affinity. In laboratory and clinical literature the abbreviation FGF23 usually refers to the measurable circulating hormone, reported either as “intact” FGF23 (the full-length, biologically active form) or as C-terminal FGF23 (which also captures cleaved fragments).
What Class of Molecule Is It, and Where Does It Come From?
FGF23 is a single-chain glycoprotein hormone — a peptide in the broad biochemical sense, though far larger than the short synthetic peptides that dominate most peptide glossaries. It is translated as a precursor, processed intracellularly, and released into circulation, where proteolytic cleavage between the N-terminal FGF-homology domain and the C-terminal Klotho-binding tail separates active hormone from inactive fragments. Its principal source is mineralised bone tissue, but FGF23 messenger RNA and protein have been detected outside bone: researchers using immunohistochemistry described the localization of FGF23 protein in the rat hypothalamus, indicating expression in central nervous system tissue as well as skeleton (PMID 34184338). Cardiac tissue has also been studied as a local source, and a 2025 animal study reported that deletion of cardiac FGF23 beneficially impacted myocardial energy metabolism in left ventricular hypertrophy (PMID 41152461).
How the Term Is Used in Peptide and Endocrine Research
In the published literature, FGF23 appears in three main roles:
- As an endogenous hormone under study. Investigators measure its production, cleavage and receptor signalling to understand mineral metabolism.
- As a circulating biomarker. Serum intact or C-terminal FGF23 is assayed in cohorts to test whether concentrations track disease severity or outcomes.
- As a therapeutic target. A 2022 review catalogued strategies to lower FGF23 bioactivity, framing the hormone as something researchers have attempted to block or reduce rather than administer (PMID 33502502).
This last point distinguishes FGF23 from many entries in a peptide glossary. It is not a compound that appears in the research-chemical literature as an administered agent; the verified studies summarised here treat it as a naturally occurring signal that is measured, genetically deleted in animals, or antagonised — not as a product given to humans.
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Try it freeWhat the Published Literature Reports
Mineral and electrolyte handling
FGF23's canonical function is phosphate regulation, and studies have extended that role to other minerals. A 2022 physiological study reported that fibroblast growth factor-23 and parathyroid hormone suppressed small intestinal magnesium absorption, linking the hormone to divalent cation handling beyond phosphate alone (PMID 35385223).
Bone and cartilage biology
Because FGF23 originates in bone, its effects on skeletal cell behaviour have been examined in vitro. In a 2017 cell-culture study, researchers reported that FGF23 promoted terminal differentiation of ATDC5 cells, a chondrogenic murine cell line used as a model of growth-plate cartilage maturation (PMID 28406928).
Kidney disease and transplantation
The largest body of clinical FGF23 literature concerns kidney function. A 2023 cohort analysis reported that FGF23, but not copeptin, was independently associated with kidney failure and mortality in patients with chronic kidney disease (PMID 38046034). In transplant recipients, a 2020 study examined erythropoietin and FGF23 in relation to death after kidney transplantation (PMID 32512806). Paediatric work has followed the same theme: a 2022 study assessed FGF23 levels alongside cardiovascular parameters in children with chronic kidney disease (PMID 34767187).
Cardiovascular outcomes
Beyond nephrology cohorts, FGF23 has been tested as a prognostic marker in acute cardiac events. A 2022 study evaluated FGF23 and outcome prediction in patients with acute myocardial infarction (PMID 35160052). The animal genetics work noted above, in which cardiac FGF23 was deleted, reported an impact on myocardial energy metabolism in the setting of left ventricular hypertrophy (PMID 41152461).
Iron, erythropoietin and hypoxia signalling
FGF23 production is not governed by phosphate alone. A 2019 review summarised the regulation of fibroblast growth factor 23 by iron, erythropoietin (EPO) and hypoxia-inducible factor (HIF), describing how these stimuli influence FGF23 transcription and cleavage (PMID 31218207). This regulatory link is one reason FGF23 and erythropoietin were examined together in the kidney transplantation cohort (PMID 32512806).
Reference values and acute illness
Interpreting an FGF23 measurement requires knowing what is typical. A 2021 study characterised serum intact fibroblast growth factor 23 in a healthy paediatric population (PMID 34258392). FGF23 has also been measured in acute infection: a 2023 observational study examined fibroblast growth factor 23 in COVID-19 (PMID 37637614).
Contexts in Which FGF23 Has Been Studied
| Context | Study type | Reference |
|---|---|---|
| Chondrocyte terminal differentiation | Cell culture (ATDC5) | PMID 28406928 reported promotion of terminal differentiation |
| Intestinal magnesium absorption | Physiological study | PMID 35385223 reported suppression with parathyroid hormone |
| Chronic kidney disease outcomes | Clinical cohort | PMID 38046034 reported independent association with kidney failure and mortality |
| Kidney transplantation | Clinical cohort | PMID 32512806 examined FGF23, EPO and death after transplantation |
| Acute myocardial infarction | Clinical cohort | PMID 35160052 evaluated FGF23 for outcome prediction |
| Brain tissue expression | Rat immunolocalisation | PMID 34184338 localised FGF23 protein in the hypothalamus |
| Paediatric reference range | Observational | PMID 34258392 measured serum intact FGF23 in healthy children |
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Get the appSafety and Adverse Events: What Studies Report
Because the verified literature treats FGF23 as an endogenous hormone rather than an administered compound, it does not describe adverse events from giving FGF23 to people, and no human dosing protocol appears in these papers. What the clinical studies reported instead were associations between higher circulating concentrations and worse outcomes: the chronic kidney disease cohort reported an independent association between FGF23 and both kidney failure and mortality (PMID 38046034), and the transplantation analysis examined FGF23 in relation to death after kidney transplantation (PMID 32512806). Association in observational cohorts does not establish that the hormone caused those outcomes. The 2022 review of strategies to lower FGF23 bioactivity discussed the approaches investigators have proposed for reducing its signalling and the open questions that remain (PMID 33502502).
Related Terms
- α-Klotho — the obligate co-receptor that confers FGF23 specificity on FGF receptors.
- Intact vs. C-terminal FGF23 — two assay formats; the first measures full-length hormone, the second also detects cleaved fragments.
- Endocrine FGFs (FGF19 subfamily) — the group of FGFs, including FGF23, that act as circulating hormones.
- Phosphate and vitamin D metabolism — the physiological axis FGF23 is best known for regulating.
This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question, laboratory result or treatment decision. Nothing here describes a protocol or endorses any use of any substance.
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Start learning freeReferences
- Fibroblast-growth factor 23 promotes terminal differentiation of ATDC5 cells (PLoS One, 2017)
- Fibroblast growth factor-23 and parathyroid hormone suppress small intestinal magnesium absorption (Physiological Reports, 2022)
- Fibroblast Growth Factor 23 in COVID-19: An Observational Study (Cureus, 2023)
- Localization of fibroblast growth factor 23 protein in the rat hypothalamus (European Journal of Neuroscience, 2021)
- Erythropoietin, Fibroblast Growth Factor 23, and Death After Kidney Transplantation (Journal of Clinical Medicine, 2020)
- Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease (Clinical Kidney Journal, 2023)
- Serum intact fibroblast growth factor 23 in healthy paediatric population (Open Medicine, 2021)
- Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy (npj Metabolic Health and Disease, 2025)
- Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF (Current Molecular Biology Reports, 2019)
- Fibroblast Growth Factor 23 Level and Cardiovascular Parameters in Children with Chronic Kidney Disease (Indian Journal of Pediatrics, 2022)
- Strategies to lower fibroblast growth factor 23 bioactivity (Nephrology Dialysis Transplantation, 2022)
- Fibroblast Growth Factor 23 and Outcome Prediction in Patients with Acute Myocardial Infarction (Journal of Clinical Medicine, 2022)
Frequently asked questions
Is FGF23 a peptide or a protein?▾
Both descriptions are used. FGF23 is a single-chain glycoprotein hormone, much larger than short synthetic peptides but still a peptide chain in the biochemical sense. It belongs to the endocrine FGF19 subfamily and circulates in blood. Researchers localised FGF23 protein in rat hypothalamic tissue using immunohistochemistry, showing expression beyond bone (PMID 34184338).
Where is FGF23 produced in the body?▾
Its principal source is bone, where osteocytes and osteoblasts secrete it into circulation. Expression has also been described elsewhere: a rat study reported localization of FGF23 protein in the hypothalamus (PMID 34184338), and an animal study in which cardiac FGF23 was deleted reported an impact on myocardial energy metabolism in left ventricular hypertrophy (PMID 41152461).
What does FGF23 do in mineral metabolism?▾
FGF23 is best known for regulating phosphate excretion and vitamin D metabolism through kidney signalling that requires the co-receptor alpha-Klotho. Its role extends to other minerals as well: a physiological study reported that fibroblast growth factor-23 and parathyroid hormone suppressed small intestinal magnesium absorption (PMID 35385223), linking the hormone to divalent cation handling in the gut.
Why is FGF23 measured in kidney disease research?▾
Circulating FGF23 rises in impaired kidney function and has been tested as a prognostic marker. A cohort study reported that FGF23, but not copeptin, was independently associated with kidney failure and mortality in chronic kidney disease (PMID 38046034). Another analysis examined erythropoietin and FGF23 in relation to death after kidney transplantation (PMID 32512806).
Has FGF23 been studied outside the kidney?▾
Yes. Researchers evaluated FGF23 for outcome prediction in patients with acute myocardial infarction (PMID 35160052) and assessed FGF23 alongside cardiovascular parameters in children with chronic kidney disease (PMID 34767187). A cell-culture study reported that FGF23 promoted terminal differentiation of ATDC5 chondrogenic cells (PMID 28406928), and an observational study examined FGF23 in COVID-19 (PMID 37637614).
What regulates how much FGF23 the body makes?▾
Phosphate and vitamin D are classical regulators, but they are not the only ones. A review summarised the regulation of fibroblast growth factor 23 by iron, erythropoietin and hypoxia-inducible factor, describing how these signals influence FGF23 transcription and cleavage (PMID 31218207). That iron–erythropoietin link informed cohort work measuring erythropoietin and FGF23 together (PMID 32512806).
Is FGF23 used as an administered research peptide?▾
The verified literature does not describe FGF23 being given to people as a compound; it is studied as an endogenous hormone that is measured, genetically deleted in animal models, or targeted for suppression. A review catalogued strategies to lower FGF23 bioactivity (PMID 33502502). Reference values for serum intact FGF23 in healthy children have also been reported (PMID 34258392).
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References
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.