NPY4R is a G protein-coupled receptor that binds pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY) with differential affinities, with PP showing the highest affinity. The receptor is negatively coupled to cAMP signaling and is expressed across diverse tissues including the pancreas, hypothalamus, hippocampus, and retina, where it modulates somatostatin secretion and appetite regulation. Genetically, NPY4R shows complex copy number variation (CNV) associated with obesity pathogenesis. Copy number losses in the 10q11.22 region containing NPY4R occur at higher frequency in children and adolescents with obesity, and rare non-synonymous variants can impair receptor function 1. Notably, in women, higher NPY4R copy number correlates positively with increased body mass index and waist circumference, with each additional copy associated with approximately 2.6 kg/m² higher BMI 2. The ancestral human copy number is approximately 4 per genome 3. Clinically, PP activating NPY4R induces satiety, suggesting therapeutic potential in obesity and type 2 diabetes, particularly through sustained Y4 receptor activation to improve insulin secretory function 4. In breast cancer patients, decreased NPY4R expression correlates with shorter relapse-free survival 5. NPY4R has been identified as a candidate gene in familial essential tremor through genome-wide linkage analysis 6. TM30339 represents a targeted approach to Y4 receptor modulation for metabolic disease.