Cathelicidins are a ubiquitous family of host defence peptides in vertebrate animals. Unlike other HDP families, they are defined by the common and relatively well conserved pro-region rather than the mature active peptides, which are highly diverse and conform to at least five different structural groups. They seem to have followed a rather distinctive evolutionary path in their development. Cathelicidin-derived peptides play a relevant role in defending the host against microbial infection, both by displaying a broad-spectrum, direct antimicrobial activity and the capacity to modulate other host responses to infection and injury. Both types of effects depend on the structural type, which in turn affects the particular mode-of-action of each peptide. This chapter begins by briefly describing the discovery of cathelicidins and then discusses their molecular diversity, also considering their evolution. It then considers their expression and processing, the structure-dependence of the distinct modes of action shown by different members, and briefly touches on their pleiotropic roles in modulating host defence.
