The underlying genes responsible for defensin production are highly polymorphic. Some aspects are conserved, however; the hallmarks of a β-defensin are its small size, high density of cationic charge and six-cysteine-residue motif. Generally they are encoded by two-exon genes, where the first exon encodes for a hydrophobic leader sequence and the second for a peptide containing the cysteine motif.

There are three main (known) forms of mammalian defensins; α-defensins, β-defensins, and θ-defensins. It is theorised that some of the pathology of cystic fibrosis arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content.