Hephaestin (HEPH)

Hephaestin is a multi-copper oxidase critical for cellular iron homeostasis, functioning as a membrane-associated enzyme that oxidizes ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), thereby facilitating iron export from intestinal epithelial cells into the blood[1][2][3][4]. This oxidation is necessary for loading iron onto transferrin, the plasma iron transport protein. Hephaestin acts as an indispensable partner of ferroportin, the principal iron exporter, and its expression is particularly prominent in the intestines, though it is also relevant in the brain, placenta, and tumor microenvironments[1]. Genetic defects in HEPH result in impaired iron absorption, leading to microcytic anemia and local iron overload. HEPH shares significant homology and similar mechanistic properties with ceruloplasmin, another multicopper ferroxidase, but is distinguished by its membrane-anchored C-terminus[2][3]. Alterations in hephaestin function or expression can impact overall iron homeostasis, contributing to disease states ranging from anemia to neurodegeneration and chemoresistance in cancer[1]. There are currently no approved drugs that specifically target hephaestin, and most known modulators are experimental tools or chelators affecting copper content essential for its activity[2].

Other names

HephaestinHEPHKIAA0698UNQ2562/PRO6242HpCPL

Inhibition of copper-dependent ferroxidase activity (for chelators like D-penicillamine)