HAMP and Tangier disease: The central role of the BMP-SMAD pathway in hepcidin regulation and systemic iron balance is further supported by the fact that mutations in the genes encoding the ligand BMP6 [18], [34], BMP type I receptors ALK2 and ALK3 [35], or common-mediator SMAD4 [36] all lead to hepcidin deficiency and iron overload similar to HJV mutations.