GPR139 (G protein-coupled receptor 139) is a protein that in humans is encoded by the GPR139 gene. GPR139 is an orphan G-protein–coupled receptor expressed in the central nervous system.

The expression pattern of GPR139 has primarily been studied on the mRNA level and showed expression mainly in the central nervous system.

GPR139 is an orphan receptor identified from bioinformatics analysis of the human genome. GPR139 is thus a potential target for the treatment of Parkinson’s disease, obesity, eating disorders, and/or diabetes.

The GPR139 is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. GPR139 agonists dose-dependently protect primary dopaminergic (DA) neurons against MPP⁺ toxicity.