The most important role of transferrin receptor (TFRC) is to carry out transport of iron bound to transferrin, which is essential for maintaining cellular iron homeostasis. After binding to transferrin, TFRC undergoes endocytosis into membrane vesicles. In the endosomes, iron is released and the complex of transferrin and TFRC is recycled to the cell membrane. A small part of TFRC is degraded in the lysosomes by autophagy. TFRC-mediated signaling induced by binding of transferrin results in the activation of some kinases including FYN, SRC, ERK-1/ERK-2, and AKT. Transferrin-induced signaling mediates the differentiation and survival of neurons. TFRC facilitates the endocytosis of other receptors, neurotropic Rabies virus, and some other viruses. Endocytic trafficking and recycling, and degradation of TFRC by autophagy are regulated by the adaptor protein OPTN (optineurin), which seems to function as a molecular switch. Glaucoma-causing OPTN mutations alter recycling and autophagy-mediated degradation of TFRC that leads to the apoptosis of retinal ganglion cells. TFRC deficiency in parvalbumin-positive interneurons leads to functional defects in mice similar to hereditary spastic paraplegia, a neurodegenerative disorder. Thus, TFRC performs vital functions in neuronal cells which are dependent on endocytosis, signaling, and iron transport.