GPR39 (G-protein coupled receptor 39) is an orphan GPCR receptor from ghrelin/motilin receptor subfamily of G-protein coupled receptor 1 family, and it is constitutively active with Zn2+ as its physiological agonist. GPR39 is a multipass transmembrane protein found in cell membranes and is expressed in several tissues such as stomach, intestine and hypothalamus. Obestatin, a 23 amino acid peptide originating from ghrelin precursor, was originally shown to be the endogenous ligand of GPR39, a study that happened to be non-reproducible, and later on it was shown that obestatin does not bind, nor activate GPR39 but that Zn2+ could stimulate GPR39 signalling in vitro, thereby inferring that obestatin is not the natural ligand of GPR39. GPR39 receptor also displays a strong ligand-independent signaling activity through G-alpha12/13 as well as G-alphaq. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. GPR39 has been shown to implicate in the regulation of insulin release/pancreatic function, body weight, gastrointestinal mobility, hormone secretion and cell death.