Most antimicrobial peptides come in families. Mice carry several cathelicidins, cattle carry more than a dozen, and pigs have their own set. Humans have exactly one, and its name is LL-37. That single peptide has been the subject of thousands of papers since researchers first pieced together its sequence in the mid-1990s. This is the story of how it was found, named, and studied.
What is LL-37 cathelicidin?
LL-37 is a 37-residue peptide, and it is the only cathelicidin the human body produces. The name is a piece of shorthand: the mature sequence begins with two leucine residues (the “LL”), and it runs 37 amino acids long. It is cationic, meaning it carries a positive charge, and it folds into an alpha-helix when it meets a membrane surface, with its water-repelling residues gathered on one face.
The peptide does not start life as LL-37. It is the C-terminal fragment of a larger precursor protein called hCAP18, encoded by the gene now known as CAMP. That precursor carries a signal peptide, a conserved “cathelin-like” domain that gives the whole family its name, and the antimicrobial fragment tucked at the end. LL-37 only appears once the precursor is cut.
The mid-1990s: naming a human cathelicidin
The peptide was first predicted from sequence rather than isolated whole. In a 1995 study published in the Proceedings of the National Academy of Sciences, Birgitta Agerberth and colleagues described a putative human peptide antibiotic they called FALL-39, named for its first four residues (F, A, L, L) and a predicted length of 39 amino acids. They reported it was cysteine-free and expressed in bone marrow and testis, and noted activity against both gram-positive and gram-negative bacteria in their tests.
The following year, in a 1996 paper in the European Journal of Biochemistry, Gudmundsson, Agerberth and co-workers characterised the human gene (they wrote it FALL39) and worked out how the cathelin precursor is processed in granulocytes. The mature peptide recovered from cells was 37 residues, two shorter than the original prediction and beginning with the two leucines. That is where the name LL-37 comes from, and it is the label that stuck.
Working out how the peptide is made
Naming the peptide was one thing; explaining how the body releases it was another. Through the late 1990s and into the 2000s, researchers traced the precursor hCAP18 to neutrophils, where it is stored, and to epithelial cells. The cathelin-like domain had to be removed for the antimicrobial fragment to be freed.
A 2001 study in the journal Blood, by Sorensen and colleagues, reported a key step in that pathway: in neutrophils, hCAP18 is cleaved outside the cell by the enzyme proteinase 3, releasing LL-37 from the precursor. The finding helped explain how a stored, inactive protein becomes an active peptide at the right place and time. Work in other species had shown different enzymes doing similar jobs, which underlined that the human system was its own case rather than a copy of the animal cathelicidins studied earlier.
From antimicrobial to immunomodulatory research
Early interest treated LL-37 mainly as a direct antimicrobial, a peptide that disrupts bacterial membranes. As the literature grew, researchers reported a wider set of activities in laboratory and animal models. Studies described roles in signalling to immune cells, in influencing cell migration, and in wound-healing models, which is why later reviews tend to call it a “multifunctional” or “immunomodulatory” peptide rather than a simple antibiotic.
That broader picture also brought complexity. Some studies reported context-dependent effects, where the same peptide behaved differently depending on concentration, tissue, or the presence of other molecules. Papers through the 2010s and 2020s have examined LL-37 in the setting of inflammation, infection models, and other conditions. This body of work remains largely preclinical: it describes what researchers have observed in cells and animals, not established outcomes in approved human treatment.
Where the research stands
Three decades on from the FALL-39 paper, LL-37 is one of the more heavily studied human antimicrobial peptides, and its basic biology, the CAMP gene, the hCAP18 precursor, and the cleavage into a 37-residue helix, is well documented. What it does across different biological settings is still an active question, and much of the newer literature is exploratory. LL-37 is a research compound, not an approved medicine, and the honest summary is that its history is better settled than its full function.
Research use only. LL-37 is supplied strictly as a research compound for laboratory investigation, and is not intended for human or animal use. Every batch is independently third-party lab-tested for identity and purity, with a published Certificate of Analysis (COA) available.