A similar autocrine Fpn regulation by Hepc has been reported in human monocytes, in cardiomyocytes, and in prostate cancer.32, –34 In the primary iron overload mouse models resulting from systemic HepcKO-, Bmp6KO-, and Hepc-resistant Fpn-knockin, all of which harbor defects in the Hepc/Fpn regulatory axis, this hypothesized autocrine loop would be impaired, consistent with the NSR iron accumulation, and lack of rVEC iron accumulation, observed in these models. This evidence concerns the gene HAMP and Tangier disease.