NPY1R is a G protein-coupled receptor that binds neuropeptide Y (NPY) and peptide YY (PYY) with high affinity, mediating adenylate cyclase-inhibiting signaling pathways 1. Beyond its classical role in energy homeostasis, NPY1R has emerged as a multifunctional receptor with significant disease relevance. In pancreatic cancer, NPY/NPY1R signaling promotes metastasis; genetic and pharmacological NPY1R inhibition with BIBO3304 substantially reduces liver metastasis in mouse models 2. In breast cancer, NPY1R expression is highest in Luminal A tumors and mediates inhibitory effects of NPY on estradiol-stimulated growth; elevated NPY1R expression predicts better endocrine sensitivity and survival in ER+ breast cancer patients 1. NPY1R also functions in gastrointestinal pain signaling, where PYY-derived NPY1R activation on enterochromaffin cells enhances serotonin release and gut sensitivity, particularly in females through estrogen-responsive pathways 3. In autoimmunity, tissue-resident Treg cells expressing NPY1R suppress pathogenic T cell responses and prevent experimental autoimmune encephalomyelitis 4. Genetically, NPY1R variants affect blood pressure regulation through altered autonomic activity 5. These findings establish NPY1R as a pleiotropic receptor with therapeutic potential across cancer, gastrointestinal, cardiovascular, and autoimmune disorders.