LL-37: The Human Cathelicidin Peptide

LL-37 is a 37-amino-acid antimicrobial peptide and the only cathelicidin encoded in the human genome. It is cut from the C-terminus of a larger precursor protein, hCAP-18, by the protease proteinase 3, and it is found in neutrophils and in epithelial cells. The peptide is strongly cationic (net charge about +6 at neutral pH), with a molecular weight of about 4493 g/mol, and it folds into an amphipathic helix when it meets membranes or certain anions.

Unlike many peptides sold for research, LL-37 is a natural human molecule with a well-mapped gene, a known processing pathway and a large academic literature. This profile covers its identity, how it was discovered, its structure, the molecular activities described in the literature, its regulatory status, and the practical points that follow from its chemistry when it is used in a lab.

Identity at a glance

Values are from PubChem (CID 16198951) and UniProt (P49913).

The name is descriptive: the peptide begins with two leucines (LL) and is 37 residues long.

The composition explains most of its behavior. There are 11 basic residues (six lysines and five arginines) against five acidic ones (two aspartates and three glutamates), which gives a net charge of about +6 at neutral pH. There are four phenylalanines, and hydrophobic residues alternate with charged ones along much of the chain. There is no cysteine, so no disulfide bonds, and no tryptophan or tyrosine, which means the peptide absorbs very little light at 280 nm. For background on how sequence and charge shape a peptide, see what peptides are.

Where LL-37 comes from

The gene and the precursor

The CAMP gene encodes an 18 kDa protein called hCAP-18 (human cationic antimicrobial protein of 18 kDa). UniProt describes the 170-residue precursor as a signal peptide (residues 1 to 30), a cathelin-like domain (31 to 131), and the antimicrobial peptide region at the C-terminus. Cathelicidins as a family are defined by that conserved cathelin-like domain; it is the C-terminal peptide that varies between species.

The peptide was first predicted in 1995 by Agerberth, Gudmundsson and colleagues from a human bone marrow cDNA and named FALL-39, after its first four residues and its length. In 1996, Gudmundsson and colleagues characterized the complete gene, a compact 1,963 base pair sequence with four exons, in which exons 1 to 3 encode the signal sequence and cathelin region and exon 4 encodes the mature peptide. They concluded that it is the only member of the cathelin gene family in the human genome, and when they isolated the mature peptide from granulocytes, its structure turned out to be two residues shorter than predicted. That mature form is LL-37 (residues 134 to 170, where FALL-39 is 132 to 170).

Processing by proteinase 3

The precursor is stored in neutrophil granules, and the peptide is released by cleavage. Sørensen and colleagues (2001) showed that hCAP-18 is not cleaved inside the phagolysosome after phagocytosis but is cleaved in exocytosed material, and that of the three serine proteases from azurophil granules, proteinase 3 alone was responsible. In other species, such as cattle and pigs, cathelicidins are cleaved by elastase instead, which was an early example of the same family being processed differently across species.

Further processing produces shorter forms. UniProt lists several fragments generated in sweat, including KR-20, LL-23, LL-29, KS-30, RK-31 and FF-33, which differ in their measured antimicrobial activity. A 12-residue segment, KR-12 (residues 18 to 29 of LL-37), was identified by Wang in 2008 as the smallest fragment with antibacterial activity.

Regulation by vitamin D

Gombart and colleagues (2005) found a vitamin D response element in the CAMP promoter that is bound by the vitamin D receptor, and showed that 1,25-dihydroxyvitamin D3 induces CAMP expression in human myeloid cell lines, keratinocytes and bone marrow-derived macrophages. The element sits in a sequence conserved in primates but absent from mouse, rat and dog genomes, and the induction was not seen in murine cells. That species difference matters for anyone translating findings between human cells and rodent models.

Structure

LL-37 does not have a single fixed shape; its conformation depends on its environment.

• In water. Johansson and colleagues (1998) used circular dichroism to show that at micromolar concentration in pure water, LL-37 is largely disordered.
• With anions. Adding 15 mM bicarbonate, sulfate or trifluoroacetate converted it to a helical structure, while 160 mM chloride was less efficient. Helicity also rose cooperatively with peptide concentration, consistent with the formation of an oligomer.
• With pH. Below pH 5 the helical content fell, and at pH 2 the peptide was entirely disordered. It remained helical above pH 13.
• In membrane mimetics. Wang's 2008 NMR structure in detergent micelles shows a curved amphipathic helix-bend-helix spanning residues 2 to 31, with the bend between Gly14 and Glu16 and a disordered C-terminal tail. The phenylalanine rings and arginines contacted the lipid, placing the whole amphipathic helix at the membrane surface.

The Johansson study also linked helicity to activity: the degree of alpha-helix correlated with antibacterial activity against both Gram-positive and Gram-negative bacteria.

Molecular activities described in the literature

LL-37 has been studied for a wide range of activities. The best-characterized are:

• Membrane activity against bacteria. UniProt summarizes in-vitro evidence that LL-37 binds bacterial lipopolysaccharide and permeabilizes membranes by forming transmembrane pores. Johansson reported a minimal inhibitory concentration against E. coli of 5 µM, cytotoxicity toward several eukaryotic cell types at 13 to 25 µM, and inhibition of both activities in the presence of human serum.
• A receptor on immune cells. De Yang and colleagues (2000) showed that LL-37 is chemotactic for human monocytes, neutrophils and T cells and induces calcium mobilization through formyl peptide receptor-like 1 (FPRL1, now called FPR2), a G protein-coupled receptor, including in HEK 293 cells transfected with that receptor.
• Complexes with self-DNA. Lande and colleagues (2007) reported that LL-37 binds self-DNA into aggregated, condensed structures that are taken up by plasmacytoid dendritic cells and trigger interferon production through Toll-like receptor 9, and identified this pathway in psoriatic skin.

These activities are described in cell systems, isolated membranes and tissue samples. They show what the molecule does in defined experiments, not an outcome in a person.

Regulatory status

LL-37 is not an approved drug in the United States. FDA had placed "Cathelicidin LL-37" in Category 2 of its interim compounding policy, the group of nominated bulk substances with significant safety concerns. FDA's page for that category, updated April 22, 2026, lists it among nominations withdrawn by the nominators, and records FDA's concerns: a risk of immunogenicity for certain routes, complexities with peptide-related impurities, and nonclinical research findings that the agency says suggest detrimental effects on male reproduction. LL-37 is not on the 503A bulks list.

LL-37 has an International Nonproprietary Name, ropocamptide, and a small number of early-phase human studies have been registered on ClinicalTrials.gov, among them a Phase 1/2 study at M.D. Anderson Cancer Center (NCT02225366). Registration does not indicate approval, and no LL-37 product has been approved.

The World Anti-Doping Agency's 2026 Prohibited List does not name LL-37.

Anhydrolabs supplies LL-37 for in-vitro laboratory research only, not for human or veterinary diagnosis, treatment, or consumption. The terms are on the research-use page.

LL-37 in the lab

Anhydrolabs supplies LL-37 as a lyophilized powder in vacuum-sealed vials. Several other catalog compounds are also available as 10-vial kits. LL-37 is made by solid-phase synthesis, and at 37 residues it is at the longer end of what is routinely produced that way; how peptides are made explains why length matters for purity.

The published chemistry points to a few specific practices:

• Record the solvent and keep it constant. Because LL-37 changes from disordered to helical, and forms oligomers, depending on anions, pH and concentration, the stock solvent and assay buffer are part of the experiment. The same peptide can behave differently in pure water, in a phosphate or bicarbonate buffer, and in a saline medium.
• Account for serum. Johansson and colleagues found that human serum inhibited both the antibacterial and cytotoxic activity of LL-37. Serum-containing culture medium is therefore not a neutral background for this peptide.
• Quantify with care. With no tryptophan or tyrosine, absorbance at 280 nm is a poor way to measure concentration. Net peptide content from the certificate, or amino acid analysis, is a better basis. At 4493 g/mol, 1 mg of peptide is about 0.22 µmol.
• Counter-ions. A cationic peptide with 11 basic residues carries many counter-ions after synthesis and purification, often acetate or trifluoroacetate. They add to the gross mass of the powder, which is why net peptide content can be well below the vial mass.
• Identity and purity. Mass spectrometry of a peptide this size shows a series of multiply charged ions; the deconvoluted mass should match 4490.58 Da (monoisotopic) or about 4493 (average). Reversed-phase HPLC reports purity as the area of the principal peak relative to all detected signal, and the related impurities of a 37-mer typically include deletion sequences one residue short. Peptide purity covers how to read those figures.
• Storage. Keep sealed powder frozen, dry and protected from light; let the vial reach room temperature before opening; divide stocks into single-use aliquots. Details are in the storage and handling guide.