Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct antimicrobial activity, immune signalling activities, or both. They are variously active against bacteria, fungi and many enveloped and nonenveloped viruses. They are typically 18-45 amino acids in length, with three or four highly conserved disulphide bonds. In animals, they are produced by cells of the innate immune system and epithelial cells, whereas in plants and fungi they are produced by a wide variety of tissues. An organism usually produces many different defensins, some of which are stored inside the cells (e.g. in neutrophil granulocytes to kill phagocytosed bacteria), and others are secreted into the extracellular medium. For those that directly kill microbes, their mechanism of action varies from disruption of the microbial cell membrane to metabolic disruption. Varieties The name 'defensin' was coined in the mid 1980s, though the proteins have been variously called 'Cationic Antimicrobial Proteins', 'Neutrophil peptides', 'Gamma thionins' amongst others. Proteins called 'defensins' are not all evolutionarily related to one another. Instead fall into two broad superfamilies, each of which contains multiple families. One superfamily, the trans-defensins, contains the defensins found in humans and other vertebrates as well as some invertebrates. The other superfamily, cis-defensins, contains the defensins found in invertebrates, plants and fungi. The superfamilies and families are determined overall tertiary structure and each family usually has a conserved pattern of disulphide bonds. All defensins form small and compact folded structures, typically with a high positive charge that are highly stable due to the multiple disulphide bonds. In all families, the underlying genes responsible for defensin production are highly polymorphic. Trans-defensins Vertebrate defensins are primarily α-defensins and the β-defensins. Some primates additionally have the much smaller θ-defensins. In general, both α- and β-defensins are encoded by two-exon genes, where the first exon encodes for a hydrophobic leader sequence (that is removed after translation) and the cysteine-rich sequence (the mature peptide). The disulfide linkages formed by the cysteines have been suggested to be essential for activities related to innate immunity in mammals, but are not necessarily required for antimicrobial activity. Theta defensins form a single beta hairpin structure and therefore also represent a distinct group. Only alpha and beta defensins are expressed in humans. Although the most well-studied defensins are from vertebrates, a family of trans-defensins called 's' are found