GPR146 is an orphan G-protein coupled receptor that belongs to the class A of seven-transmembrane GPCR superfamily. The endogenous ligand for GPR146 is not known. It has been suggested that GPR146 may be a part of the C-peptide signaling complex [].All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes [, ].