NPY2R (neuropeptide Y receptor Y2) is a G-protein-coupled receptor that primarily functions as a receptor for neuropeptide Y (NPY) and peptide YY (PYY), with preferential binding affinity for PYY 1. The receptor mediates adenylate cyclase-inhibiting signaling and regulates multiple physiological processes including food intake, cardiac function, and immune responses. Mechanistically, NPY2R activation suppresses energy intake and gastric emptying 2, while in cardiac contexts, NPY2R-expressing vagal sensory neurons mediate the Bezold-Jarisch reflex—a cardioinhibitory response producing hypotension, bradycardia, and syncope 3. NPY2R also plays a pathogenic role in kidney disease, where excessive NPY-NPY2R signaling in podocytes promotes albuminuria through PI3K, MAPK, and NFAT activation 4. Additionally, NPY2R in vagal sensory neurons transmits tumor-derived signals to the brainstem, driving sympathetic output that suppresses anti-tumor immunity 5. Genetjc variations in NPY2R associate with obesity susceptibility; SNPs in the 5' region and intron 1 show significant associations with BMI that are additive to other obesity genes 6, 7, 8. NPY2R agonists like BI 1820237 show promise for obesity treatment, particularly when combined with GLP-1R/GCGR dual agonists 2. Inhibiting NPY2R signaling reduces albuminuria and may provide therapeutic benefit in kidney disease 4.