NPY is a highly conserved neuropeptide widely distributed throughout the central nervous system that functions as a critical regulator of stress response, feeding behavior, and emotional processing 1. As a G protein-coupled receptor ligand, NPY signals through multiple receptor subtypes (Y1, Y2, Y4, Y5) to modulate physiological processes 2. Structurally, human NPY adopts a four-helix bundle arrangement with propensity for multimerization, distinct from other pancreatic polypeptide family members 3. NPY exerts vasoconstrictive effects in peripheral tissues, with NPY-immunoreactive fibers distributed around cerebral and nasal mucosal blood vessels where they regulate vasomotor tone 4. Clinically, NPY system dysfunction is implicated in depression and suicidal behavior; postmortem studies of depressed suicide subjects revealed significantly decreased NPY mRNA and protein expression in the prefrontal cortex and hippocampus, coupled with upregulated NPY receptor expression 1. These findings suggest impaired NPY signaling contributes to depressive pathophysiology 5. In adipose tissue, NPY-Y1 receptor activation produces antilipolytic effects and stimulates leptin secretion, linking NPY to metabolic regulation 2. The convergence of evidence across neural and peripheral tissues positions NPY as a therapeutic target for depression and metabolic disorders.