Epiregulin was initially identified as a growth-inhibitory factor from the conditioned medium of the murine tumor cell line NIH3T3/clone T7. It belongs to the EGF family of proteins that includes EGF, TGF-α, heparin-binding EGF like-growth factor (HB-EGF), epigen, epiregulin, betacellulin, neuroregulin, and tomoregulin. It posesses 24-50% amino acid sequence identity with sequences of other EGF-related growth factors. All the EGF family members are synthesized as type I membrane protein precursors, which can undergo proteolytic cleavage at the plasma membrane to release a mature soluble ectodomain. Epiregulin acts as an autocrine growth factor in human epidermal keratinocytes, and it can be induced by HB-EGF, amphiregulin, and TGF-α. Epiregulin is expressed by, and plays a key role in, immune-related responses of keratinocytes and tissue resident macrophages. It has been shown that epiregulin-deficient (EP-/-) mice develop chronic dermatitis. Also, epiregulin is involved in proinflammatory cytokine production in bone marrow-derived macrophages. In addition, epiregulin induces proliferation of human corneal epithelial cells and its expression can be induced in these cells by TGF-α, HB-EGF, AR, and EGF. Epiregulin plays a role in the development of hyperkeratosis during the pathogenesis of middle ear cholesteatoma, and it is overexpressed in psoriatic epidermis. Epiregulin polymorphisms seem to be associated with susceptibility to different clinical phenotypes of TB, and epiregulin modulates the innate immune responses of TB.