The transferrin receptor (TfR) is a transmembrane glycoprotein that is highly expressed on multiple cell types, apart from highly differentiated cells. Two forms of the receptor have been characterised to date; TfR-1 and TfR-2, TfR-1 being the main receptor for cellular uptake of transferrin-bound iron molecules. The process by which this happens is that initially TfR-1 recognises and binds to transferrin, a plasma glycoprotein, which in turns binds circulating iron molecules with a high affinity. The transferrin-iron complexes bound to TfR-1 are then internalised via receptor-mediated endocytosis into the cell. pH changes within the cell allow for the release of the iron, which undergoes further processing and finally is stored either as haemoglobin or ferritin. The TfRs are always recycles back to the plasma membrane for continuous use.
The TfR is important for maintaining iron homeostasis within the body, and abnormal serum levels of these receptor are used as an indicator for iron deficiencies, such as anaemia.