G protein-coupled receptors (GPCRs) play a central role in mediating the intracellular effects of numerous neurotransmitters and hormones, including melatonin. GPR50, also designated Melatonin-related receptor, GPCR50 and H9, does not bind melatonin. It is a multi-pass membrane protein primarily detected in hypothalamus and pituitary. GPR50 is a 613 amino acid protein that contains the seven hydrophobic segments that are characteristic of GPCRs, as well as the distinguishing sequence motifs of the melatonin receptor GPCR family. The GPR50 protein is 45% identical to the melatonin receptors 1A and 1B and has an unusually long proline-rich C-terminal tail. Research suggests that a deletion variant within the GPR50 gene is a sex-specific risk factor for susceptibility to BPAD (bipolar affective disorder) and that other variants in the gene may be sex-specific risk factors in the development of schizophrenia.