Under physiological conditions, Trf binds to ferric ion and delivers it to a variety of tissues (eg, the liver) for iron requisition and use. When hepatic Trf is absent, affected individuals develop microcytic anemia because of iron-restricted erythropoiesis, which leads to increased iron absorption in the intestine as a consequence of erythropoietin/erythroferrone-dependent suppression of hepcidin, NTBI accumulation via Slc39a14 in multiple organs, and finally the iron overload–evoked ferroptosis, fibrosis, and cirrhosis. EPO, erythropoietin.