The protein encoded by the HFE gene is a non-classical HLA class I-like protein which contains a signal sequence, peptide-binding extracellular domains, a trans-membran region and a small cytoplasmic portion. Within the α-2 and α-3 extracellular domains, are the four cysteine residues that form disulphide bridges representing one of the most conserved structural features of class I molecules. HFE interacts with β2 m, and this association enables efficient transport of HFE to the cell surface where it interacts with transferin receptor 1. C282Y mutation disrupts the disulphide bridges in the extracellular domains of the HFE protein, thereby preventing the association of HFE with β2 m and transferin receptor 1. The lack of HFE interaction with transferin receptor 1 increases affinity of transferin receptor 1 for the transferin-bound iron, thereby modulating iron absorption. In contrast to the C282Y mutation, mutant H63D HFE formed stable complexes with tranferin receptor 1 being in line with the clinical data that H63D HFE mutationsmmarginally affect iron absorption and rarely lead to hemochromatosis.