GALR2 (galanin receptor 2) is a G protein-coupled receptor that binds galanin, galanin-like peptide (GALP), and spexin-1 as its primary ligands 1. The receptor is located on chromosome 17.3 and encodes a 387 amino acid protein with high affinity for galanin (Kd = 0.24-0.3 nM) 21. GALR2 exhibits dual G protein coupling mechanisms: it activates phospholipase C/protein kinase C pathway via Gq/11 to increase intracellular calcium levels, and inhibits adenylyl cyclase via Gi/o proteins 13. The receptor shows wide tissue distribution in brain regions including hypothalamus, dentate gyrus, and mammillary nuclei, as well as peripheral tissues like small intestine 1. GALR2 has significant clinical relevance across multiple conditions. In cardiovascular disease, spexin acting through GALR2 reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and downregulating ion channel expression 4. The receptor is implicated in neuropathic pain control and processing, with potential therapeutic applications for pain management 5. In cancer, the GAL/GALR2 axis promotes perineural invasion in salivary adenoid cystic carcinoma through epithelial-to-mesenchymal transition 6. Additionally, GALR2 signaling appears relevant to metabolic disorders and reproductive health, with altered expression patterns observed in polycystic ovary syndrome and potential links to diabetes-Alzheimer's disease comorbidity 78.