Mutations of the TFR2 gene cause iron overload disease, hereditary hemochromatosis, and the affinity of TFR2 to holo-TF was 25-fold lower when compared with that of TFR1, indicating that TFR2 functions as an iron sensor unlike TFR1 (7, –, 9). This evidence concerns the gene TFR2 and Rare hereditary hemochromatosis.