G protein-coupled receptor family C group 5 member B (GPRC5B)

G protein-coupled receptor family C group 5 member B (GPRC5B) is a class C orphan G protein-coupled receptor, most prominently expressed in the central nervous system, where it is among the most abundant orphan GPCRs[1][2]. It is characterized by a short extracellular N-terminus and lacks the typical Venus flytrap domain found in many other class C receptors. GPRC5B is strongly implicated in neuronal signaling, neurodevelopment, and brain function, having roles in synaptic plasticity, motor learning, and possibly adult neurogenesis. Its expression is induced by retinoic acid and is also present in immune and vascular cells, with emerging data showing that it modulates prostanoid receptor trafficking and signaling, particularly the EP2 receptor, thereby influencing inflammatory and metabolic processes[1][2][3]. Pathogenic mutations in GPRC5B cause a rare form of leukodystrophy, reflecting its importance in brain physiology. No drugs are currently approved targeting GPRC5B, likely because its endogenous ligand and signaling mechanisms remain incompletely defined.

Other names

Retinoic acid-induced gene 2 proteinRAIG2RAIG-2A-69G12.1MLC3Retinoic acid inducible orphan G protein-coupled receptorretinoic acid responsive gene protein

For related prostanoid signaling: Regulates receptor trafficking and signaling (notably prostacyclin and EP2/EP1/DP1 prostaglandin receptors) - Facilitates EP2 receptor membrane localization and signaling, thus modulating cAMP production and downstream signaling[3]