NUCB2 (nucleobindin 2) encodes nucleobindin-2, a precursor protein proteolytically cleaved into nesfatin-1, nesfatin-2, and nesfatin-3 1. The primary function of NUCB2/nesfatin-1 is regulation of food intake and energy homeostasis through anorexigenic mechanisms 2. Nesfatin-1 is widely distributed in hypothalamic autonomic centers regulating feeding, and co-localizes with multiple neurotransmitters involved in metabolic control 2. Beyond appetite regulation, NUCB2/nesfatin-1 participates in stress response and emotion regulation, with immunoreactive neurons detected in the hippocampus, amygdala, and prefrontal cortex 3. Recent evidence indicates nesfatin-1 mediates stress-related gastrointestinal disorders through brain-gut crosstalk, while appearing protective against inflammatory bowel disease 4. Peripherally, NUCB2/nesfatin-1 is expressed predominantly in gastric X/A-like cells co-producing ghrelin, pancreatic endocrine cells, and the pituitary 2. NUCB2/nesfatin-1 also functions in vascular smooth muscle calcification by stabilizing BMP-2 signaling, promoting osteogenic transformation and vascular calcification through STAT3-mediated transcriptional activation 5. These multifunctional properties position NUCB2/nesfatin-1 as a candidate therapeutic target for obesity, diabetes, stress-related disorders, and cardiovascular pathology.