Understanding the detailed molecular mechanisms of BMP-SMAD pathway regulation by plasma and tissue iron and how the hepatocyte responds to a combination of different signals will increase our understanding of how systemic iron homeostasis is maintained in physiological conditions and how it is deranged in disorders due to hepcidin deregulation, exemplified by hemochromatosis, thalassemia, IRIDA, and inflammatory disorders. This evidence concerns the gene HAMP and IRIDA syndrome.