Transferrin receptor 1 exists widely in central nervous system (CNS). It is responsible for iron transport in vivo and mediates the endocytosis of transferring-iron complex, regulating the cell growth. TfR1 transports other metal ions as well, such as Mn, Al and Cu. It is proved that TfR1 can help macromolecular drugs to pass through the blood-brain barrier and emerges as a potential therapeutic target of neurological diseases in CNS. This review summarizes recent findings in distribution, function, and modulatory mechanisms of TfR1 as well as its applications as therapeutic targets in clinical medicine. The investigations on these issues can not only provide new ideas for the research about the mechanism and function of TfR1, but also have profound significance in the understanding of neuroscience.