The regulation of energetic efficiency through the physiological uncoupling of oxidative phosphorylation may be a common strategy developed early in evolution. Uncoupling protein families are transporters in mitochondrial inner membrane. There are five UCP homologs in mammalian genome. UCP1-3 are closely related with each other, while UCP4 and UCP5 (also called brain mitochondrial carrier protein-1, BMCP1) differ from them greatly. UCP1-4 were discovered not only in endotherms such as mammals and birds, but also in ectothermic vertebrates such as fish and amphibia. UCP5 was identified only in mammals. UCP1, which is only expressed in mammalian brown adipose tissue, mediates proton leakage of the proton gradient that is generated by the respiratory chain, and as a result, the oxidative energy is dissipated as heat. UCP2 and UCP3 function both in fever, ROS inhibition, fatty acid oxidation, the development of obesity and type 2 diabetes mellitus and so on. Their expression regulations are complex. UCP4 and UCP5 diverge from other UCP further. UCP4 is uniquely expressed in brain, whilst UCP5 transcripts are present in multiple tissues, with an especially high abundance in brain. Their functions are still unclear, but they have been implicated in processes similar to those suggested for UCP2 and UCP3.