GRM4 encodes metabotropic glutamate receptor 4 (mGluR4), a G-protein coupled receptor that inhibits adenylate cyclase activity upon glutamate binding. The receptor plays diverse roles beyond its classical neurotransmitter function. In neural contexts, GRM4 expression is upregulated in anxiety-related responses, with changes observed in amygdala glutamatergic signaling pathways 1. The receptor also mediates α-synuclein fibril-induced neurodegeneration through formation of an mGluR4-NPDC1 complex that facilitates α-synuclein fibril binding and internalization in dopamine neurons 2. In cancer biology, GRM4 functions as a tumor suppressor in osteosarcoma by interacting with CBX4 to restrict its nuclear localization and affect HIF-1α transcriptional activity 3. Additionally, mGluR4 serves as an immune checkpoint by suppressing dendritic cell maturation through inhibition of adenyl cyclase/PKA signaling, leading to metabolic reprogramming that affects anti-tumor immune responses 4. Genetic polymorphisms in GRM4 are associated with osteosarcoma susceptibility and prognosis in Chinese populations 5, though no significant association was found with juvenile myoclonic epilepsy 6. These findings reveal GRM4's multifaceted roles in neurodegeneration, cancer, and immune regulation.