Hepcidin and hemochromatosis. (A) The activity of hepcidin is depicted, showing ferroportin as a target both on enterocytes and macrophages. Hepcidin binds to ferroportin triggering its internalization and lysosomal degradation. (B) Three classes of hemochromatosis disorders all affect the hepcidin/ferroportin regulatory axis: Class I, defects in the hepcidin gene (HAMP) preventing production of functional hepcidin; Class II, defects in HFE, TFR2, or HFE2 genes preventing normal hepatic regulation of hepcidin expression; Class III, defects in ferroportin preventing normal regulation by hepcidin. Illustration by Kenneth Probst.