What Is LL-37? Definition and What Research Reports

Definition

LL-37 is the mature, biologically active peptide released from the C-terminal end of human cationic antimicrobial protein 18 (hCAP18), the single human cathelicidin precursor encoded by the CAMP gene. The name comes from its structure: it begins with two leucine residues and is 37 amino acids long. Like other cathelicidins, it is amphipathic and carries a net positive charge, which allows it to associate with negatively charged bacterial membranes. In the published literature the terms LL-37, human cathelicidin, hCAP18/LL-37 and cathelicidin antimicrobial peptide (CAMP) are often used interchangeably, though strictly speaking hCAP18 refers to the stored precursor and LL-37 to the cleaved fragment.

Class of Molecule and Biological Origin

LL-37 belongs to the host-defence peptide (or antimicrobial peptide) class — small, gene-encoded peptides produced by multicellular organisms as part of innate immunity. It is not a hormone, not a growth factor, and not a receptor-selective analogue of any endogenous signalling system in the way that many research peptides are. Instead, it is an effector and modulator molecule of the innate immune response.

hCAP18 is stored in the specific granules of neutrophils and is also expressed by epithelial cells of the skin, airway, oral mucosa and gut, as well as by monocytes, mast cells and other cell types. Proteolytic processing releases LL-37 at sites of infection or injury. Expression of the CAMP gene is vitamin D–responsive: researchers examining vitamin D signalling reported that vitamin D triggered hCAP18/LL-37 production in their experimental system, a link that has made LL-37 a frequently measured readout in vitamin D and innate-immunity research.

How the Term Is Used in Peptide Research

Across the literature, "LL-37" appears in several distinct research contexts, and the meaning shifts with context:

• As a biomarker. Concentrations of LL-37 in saliva, sputum, serum or tissue are measured as an index of innate immune activity. Investigators have quantified the peptide in children with post-infectious bronchiolitis obliterans alongside human β2-defensin levels in a clinical comparison, and in saliva from children and adolescents living with HIV in a study examining salivary cathelicidin in that population.
• As an antimicrobial agent and template. Because of its membrane activity, LL-37 is used as a scaffold for designing synthetic analogues. One group designed, synthesised and characterised non-hemolytic antimicrobial peptides related to human cathelicidin LL-37, explicitly aiming to retain antimicrobial character while reducing damage to red blood cells.
• As an immunomodulator. Beyond killing microbes, LL-37 interacts with host cells. Researchers examining tissue mast cells reported that LL-37 affected surface and intracellular Toll-like receptor expression, and a separate group studying airway epithelium reported that LL-37 increased rhinovirus-induced interferon β expression through a Ca²⁺-dependent mechanism.
• As a disease-associated molecule. In some conditions LL-37 is studied as a driver rather than a defender. Work on rosacea described LL-37 igniting primed NLRP3 inflammasomes, and a review of the oral cavity surveyed cathelicidin LL-37 in both health and disease states of oral tissues.
• As a delivery or engineering payload. One group engineered exosomes containing cathelicidin/LL-37 and reported multiple biological functions for the resulting particles.

What the Published Literature Reports

The research picture is best described as dual-natured: the same peptide has been reported to support antimicrobial and antiviral defence in some settings and to amplify inflammation or damage host cells in others. This is why the literature rarely treats LL-37 as a simple "good" or "bad" molecule.

Host defence and immune signalling

In airway epithelial cells, the study of rhinovirus infection reported that LL-37 increased interferon β expression via a calcium-dependent pathway, positioning the peptide as an amplifier of antiviral signalling rather than only a direct microbe-killing agent. In mast cells, researchers reported changes in both surface and intracellular Toll-like receptor expression after LL-37 exposure, consistent with a role in shaping how innate immune cells sense pathogens.

Inflammation and disease association

The rosacea work reported that LL-37 activated primed NLRP3 inflammasomes, which is one mechanistic account of why elevated cathelicidin has been linked to inflammatory skin phenotypes. In a surgical-tissue context, investigators examined cathelicidin LL-37 expression in human breast implant capsules, an example of the peptide being measured in fibrotic and foreign-body-response tissue.

Metabolic and vascular contexts

More recent work has extended LL-37 beyond immunity. One group reported that an LL-37–ApoB-100 interaction promoted LDL clearance and attenuated cholesterol accumulation in the liver in their model. Vascular work has gone the other way: researchers reported that human cathelicidin peptide LL-37 induced cell death in autophagy-dysfunctional endothelial cells, implying that the cellular context determines whether exposure is tolerated.

LL-37 in the Literature at a Glance

Cytotoxicity and Tolerability: What Studies Report

Because LL-37 is membrane-active, host-cell effects are a recurring theme. In bone cell work, the study described LL-37-induced human osteoblast cytotoxicity in the context of vitamin D–triggered peptide production. In endothelial cells, researchers reported LL-37-induced cell death when autophagy was dysfunctional. Haemolysis has been treated as a design constraint rather than an afterthought: the analogue work was framed around producing non-hemolytic peptides related to LL-37. These are laboratory and preclinical observations in defined systems; they are not statements about outcomes in people using any product.

Limitations of the Current Literature

• Much of the mechanistic work is in vitro or in animal models, where peptide concentration, buffer composition and serum content strongly influence activity.
• Human studies cited here are largely observational measurements of endogenous LL-37 in fluids or tissue such as the salivary cathelicidin study in children and adolescents living with HIV, not interventional trials of administered peptide.
• Findings are context-dependent — protective in one tissue, damaging in another — so results do not generalise across organ systems.
• There is no approved human therapeutic consisting of LL-37; the peptide appears in the literature as a research and biomarker molecule.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any health question or before making any decision related to a medical condition or treatment.

References

• Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity (Biochemical and Biophysical Research Communications, 2024)
• Cathelicidin LL-37 in Health and Diseases of the Oral Cavity (Biomedicines, 2022)
• Cathelicidin LL-37 Ignites Primed NLRP3 Inflammasomes in Rosacea (Journal of Investigative Dermatology, 2021)
• Design, synthesis, and characterization of non-hemolytic antimicrobial peptides related to human cathelicidin LL-37 (RSC Advances, 2023)
• Cathelicidin LL-37 Expression in Human Breast Implant Capsules (Plastic and Reconstructive Surgery, 2024)
• Cathelicidin (LL-37) and human β2-defensin levels of children with post-infectious bronchiolitis obliterans (The Clinical Respiratory Journal, 2017)
• Cathelicidin LL-37-ApoB-100 interaction promotes LDL clearance and attenuates cholesterol accumulation in the liver (Science China Life Sciences, 2026)
• Cathelicidin LL-37 Affects Surface and Intracellular Toll-Like Receptor Expression in Tissue Mast Cells (Journal of Immunology Research, 2018)
• Salivary Cathelicidin (LL-37) in Children and Adolescents Living with HIV (Biomedicine Hub, 2024)
• Human Cathelicidin Peptide LL-37 Induces Cell Death in Autophagy-Dysfunctional Endothelial Cells (Journal of Immunology, 2022)
• Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a Ca²⁺-dependent mechanism (Biochemistry and Biophysics Reports, 2025)
• Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions (Advanced Healthcare Materials, 2022)