Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor (TR) into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site [taken from the Universal Protein Resource (UniProt) www.uniprot.org/uniprot/P02786].