Liver conditional inactivation of Smad4 [7] or Alk3 [5] causes severe iron overload due to downregulation of hepcidin, similar to the phenotype of Hjv-/- [8,9] and Hamp-/- [10] mice, whereas liver specific deletion of Alk2 blunts the response of hepcidin to increased iron levels [5]. Here, HAMP is linked to energy intake.