Genetic disorders affect different steps of the iron regulatory loop. Schematic representation of iron homeostasis. The hepcidin regulatory pathway is indicated in blue; the erythroid pathway, in red. Activation is indicated by plus (+) and inhibition by minus (–). The question mark on the dotted arrow indicates an uncertain effect. Proteins whose gene is affected by mutations are in light green rectangles. They are marked with a blue asterisk if their alteration causes hemochromatosis and with a red asterisk if it leads to iron overload and iron-deficient erythropoiesis/anemia. DMT1 indicates divalent metal transporter 1; TFR1, transferrin receptor 1; Fe-TF, diferric transferrin; TFR2, transferrin receptor 2; FPN, ferroportin 1; CP, ceruloplasmin; dcytb, duodenal cytochrome b; and HEPH, hephaestin. Illustration by Kenneth Probst.