CD71, also known as the transferrin receptor (TFR), is a type II membrane glycoprotein that exists as a disulfide-linked homodimer of two identical subunits. CD71 binds to two molecules of transferrin and a serum iron-transport protein, and directs the cellular uptake of iron via receptor-mediated endocytosis. CD71 is expressed, typically at high levels, on all proliferating cells, reticulocytes and erythroid precursors. It is not expressed on resting leukocytes, but is upregulated upon activation of lymphocytes, monocytes and macrophages. CD71 is also found on most dividing cells and on brain endothelium. A second transferrin receptor, TFR2, also mediates the uptake of transferrin-bound iron. TFR2 is a two-subunit homodimer and is highly expressed in liver as well as in hepatocytes and erythroid precursors. Mutations in the TFR2 gene result in hereditary hemochromatosis type III (HFE3), an iron overloading disorder predominant in Caucasians.
