GRM3 encodes glutamate metabotropic receptor 3, a G-protein coupled receptor that functions as a negative regulator of adenylate cyclase activity upon glutamate binding. The receptor is expressed on neuronal and non-neuronal plasma membranes, including hypothalamic and gastric neurons, where it modulates synaptic transmission and cellular signaling through PI3K-AKT pathways 1. Primary functions include appetite regulation and gastric motility control. Raptin, a sleep-induced hormone, binds GRM3 to suppress food intake and prevent obesity through hypothalamic and gastric signaling, with deficient Raptin-GRM3 signaling linked to night eating syndrome and obesity 1. Genetically, GRM3 variants associate with schizophrenia susceptibility, though findings remain complex. Meta-analysis of 11,318 cases identified three SNPs (rs2237562, rs13242038, rs917071) with significant associations showing population-dependent effects 2, while Japanese replication studies failed to confirm previously reported associations 3. GRM3 polymorphisms predict antipsychotic treatment response, with rs274622 and rs1468412 significantly predicting negative symptom improvement and adverse working memory changes, respectively 4, 5. Additionally, GRM3 expression is reduced in glioma-related epilepsy, suggesting potential diagnostic biomarker utility 6. These findings indicate GRM3's role in metabolic, psychiatric, and neurological pathways, with clinical implications for personalized antipsychotic therapy.