Transferrin Receptor (TfR, TfR-1, CD71) is a transmembrane glycoprotein expressed on erythroid progenitors, muscle cells and proliferating cells as a disulfide-linked homodimer. As the major mediator of cellular iron uptake, it binds and internalizes diferric transferrin, allowing iron release at the low pH of the endosome. Proteolytic shedding of TfR into the circulation is enhanced by iron deficiency. The hereditary hemochromatosis protein HFE competes with diferric transferrin for binding to TfR and targets TfR for degradation rather than recycling. Cancer cells can express up to 5-fold more TfR than quiescent cells in the surrounding tissue. TfR carries out ferritin-independent functions in T cell development, immunological synapse formation and Galectin-3-mediated cell death, and it serves as a cell entry receptor for New World hemorrhagic fever arenaviruses.