Cathelicidin family

Cathelicidins are a family of cationic host-defence peptides characterised by a conserved N-terminal cathelin domain attached to a variable C-terminal antimicrobial peptide sequence. They are produced as inactive precursors stored in neutrophil granules and epithelial cells, then activated by serine proteases upon secretion at sites of infection or injury. Humans express a single cathelicidin gene (CAMP), which produces the precursor hCAP-18; proteolytic processing releases the active C-terminal fragment LL-37.

Why it matters in peptide research

Cathelicidins, and LL-37 in particular, operate at the interface of innate immunity and tissue repair — a functionally rich position that makes them highly relevant to peptide research. LL-37's antimicrobial activity derives primarily from its amphipathic alpha-helical structure, which inserts into and disrupts bacterial, fungal, and some enveloped viral membranes. Crucially, this membrane-disrupting mechanism targets the negatively charged lipopolysaccharide-rich outer leaflet of bacterial membranes while sparing cholesterol-containing mammalian cell membranes, providing intrinsic selectivity.

Beyond direct killing, LL-37 modulates the immune response by neutralising endotoxin (LPS), promoting dendritic cell maturation, stimulating angiogenesis, accelerating wound re-epithelialisation, and acting as a chemoattractant for neutrophils, monocytes, and T cells. This makes the cathelicidin family a model system for understanding how evolution has produced molecules that simultaneously kill pathogens and orchestrate repair — properties that researchers are attempting to harness therapeutically.

The family also illustrates several key principles in antimicrobial peptide biology: the importance of secondary structure over primary sequence, the role of local ionic strength (high salt environments can abolish activity), and the regulatory influence of vitamin D on CAMP gene expression — a mechanistic link between vitamin D status and mucosal immune defence.

Peptides / stacks that act on this

• LL-37 — the sole human cathelicidin mature peptide; studied for antimicrobial activity, wound healing, anti-biofilm properties, and immunomodulation

Reading tip

Many peptides from non-human species are labelled "cathelicidin-like" in the literature based on structural or functional similarity but without a conserved cathelin domain. Exercise caution when extrapolating findings from frog, bovine, or murine cathelicidins to human LL-37 biology — the structural differences can substantially alter receptor interactions and selectivity profiles.