SLC40A1 and Tangier disease: Other conditions causing aberrant primary iron overload include inherited disorders of iron metabolism characterized by two main mechanisms: (1) the alteration of hepcidin–ferroportin interaction that induces increased intestinal iron absorption and macrophage iron release, leading to tissue iron overload; and (2) a defective expression of ferroportin on the cell membrane, due to loss-of-function mutation of SLC40A1 that impairs the iron export efficiency of ferroportin, causing iron retention in reticuloendothelial cells and hyperferritinemia with normal transferrin saturation [54].