Abstract: GPR50 is an orphan seven-transmembrane receptor known as related to the melatonin receptor subfamily which comprised of MT1, MT2 and Mel1c receptors. Previous studies implicate that GPR50 might be involved in hypothalamic control of energy expenditure and feeding behavior. GPR50 expression in brain is highly responsive to energy status as being decreased in both fasting and high fat diet feeding circumstances. GPR50-/- mice present elevated metabolic rate, reduced fat accumulation, and partial resistance to diet-induced obesity. In human, GPR50 polymorphisms have been linked to elevated circulating triglycerides and cholesterol level, as well as psychiatric affective disorders. This review presents current knowledge regarding to the functions and associated diseases of GPR50. However, GPR50 may have more functions that remain to be discovered. To reveal the signaling pathway(s) of GPR50 and its functions well, it is crucial to do more works to identify the ligand(s) of GPR50 and the possibility of ligand-dependent signaling.

Keywords: GPR50, GPCR, energy metabolism, orphan receptor