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How mutant HFE causes hereditary hemochromatosis.

In this issue of Blood , Wu et al describe the molecular function of HFE , the gene most commonly mutated in hereditary hemochromatosis (HH). 1 HH is the most frequent genetic disorder of the Western world. The authors show that HFE prevents ubiquitination and proteasomal degradation of bone-morphogenetic protein (BMP) receptor type I (Alk3), thereby increasing expression of this receptor on the cell surface of hepatocytes. As a consequence, transcription of the iron-hormone hepcidin is activated.