An orphan GPCR (GPR50) was shown to regulate bipolar-affective disorder, lipid metabolism, thermogenesis, adipogenesis, and neuronal development,21, 22, 23, 24, 25 although it has been claimed that GPR50 has high sequence similarity with melatonin receptors (MT1 and MT2), but melatonin does not bind to GPR50.19 This evidence concerns the gene GPR50 and bipolar disorder.