G protein-coupled receptor 158 (GPR158)

G protein-coupled receptor 158 (GPR158) is a member of the class C GPCR superfamily predominantly expressed in the central nervous system, where it serves as an atypical metabotropic receptor for glycine[2][5][1]. GPR158 controls synapse formation and neuronal excitability, and is implicated in mood regulation, cognition, and stress response[5][7]. Unlike classic class C GPCRs, GPR158 does not directly couple to conventional G proteins, but instead recruits and regulates the RGS7-Gβ5 complex, which modulates downstream signaling by acting on Gi/o proteins to control cAMP levels[1][2][5]. Recent studies show GPR158 is activated by glycine, with taurine acting as a weaker partial agonist, and there is emerging evidence for a role in peripheral endocrine regulation and potential involvement in glucocorticoid-induced ocular hypertension[1][2][3]. No approved therapeutics currently target GPR158.

Other names

Metabotropic glycine receptormGlyRKIAA1136Probable G-protein coupled receptor 158

Glycine binds to GPR158, altering its conformation and the associated RGS7-Gβ5 complex, resulting in regulation of cAMP production and downstream signaling pathways. Taurine acts as a partial agonist at this receptor, but with lower potency than glycine.