NPY4R is a G protein-coupled receptor that functions as a satiety-regulating receptor by binding pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) with PP showing the highest affinity 1. The receptor is negatively coupled to cAMP signaling 1, and activation by PP decreases somatostatin secretion from neuroendocrine cells across multiple tissues including pancreatic islets and hippocampus 2. Genetically, NPY4R shows substantial copy number variation (CNV) on chromosome 10.22, with the most common copy number being 4 rather than 2 3. CNV loss in this region correlates with obesity in children and adolescents 4, while increased copy number associates with higher BMI and waist circumference specifically in women, with each additional copy correlating to 2.6 kg/m² BMI increase 5. NPY4R variants identified in obese patients demonstrated receptor dysfunction 4. Beyond metabolic regulation, NPY4R has broader physiological roles: it is widely expressed in retinal neurons including photoreceptors, amacrine cells, and ganglion cells 6, and genome-wide studies identified NPY4R as a candidate gene in familial essential tremor 7. In breast cancer, decreased NPY4R expression associates with shorter relapse-free survival 8. The receptor represents a potential therapeutic target for obesity and diabetes through sustained activation 9, though short peptide half-life limits clinical development.