The present study reports that silencing Hfe and TfR2 in macrophages induced the upregulation of hepatic Hepc transcription, although it is dispensable for hepatic iron regulation, highlighting the macrophage-specific functions of these two Hereditary Hemochromatosis proteins [34,35] in the regulation of cellular and tissue iron homeostasis. The gene discussed is HFE; the disease is hereditary hemochromatosis.