GRM8 encodes a Group III metabotropic glutamate receptor, a G-protein-coupled receptor that inhibits adenylate cyclase signaling upon glutamate binding 1. As a neurotransmitter receptor responding to glutamate, GRM8 likely functions as a presynaptic modulator of glutamate release at axon terminals 1. GRM8 has emerged as a significant psychiatric susceptibility gene with well-documented associations across multiple psychiatric disorders. Genome-wide association studies identified GRM8 as a neurotransmitter synaptic modulator contributing to post-traumatic stress disorder (PTSD) pathophysiology 2. Multiple case-control studies demonstrate GRM8 polymorphisms (rs2237781, rs1361995, rs712723, rs2299472) associate with schizophrenia and major depressive disorder risk across diverse populations 345. GRM8 is implicated in attention-deficit/hyperactivity disorder (ADHD) pathogenesis 6, reflecting glutamatergic pathway dysfunction in neurodevelopmental conditions. Clinically, GRM8 dysregulation appears relevant to CNS disorders involving glutamatergic neurotransmission. GRM8 expression is induced in brain-metastatic tumor cells following neuronal contact, suggesting roles beyond psychiatric disease 7. Recent evidence links GRM8 expression changes to alcohol use disorder pathology in the central amygdala 8. These findings collectively position GRM8 as a key glutamatergic modulator relevant to psychiatric and neurological disease mechanisms, though therapeutic targeting strategies remain underdeveloped.