Human Neuropeptide Y Receptor Y2 (NPY2R) Protein

Background

NPY2R is a G protein-coupled receptor that binds neuropeptide Y (NPY) and peptide YY (PYY) with high affinity. NPY2R is predominantly expressed in the central nervous system (CNS), particularly in the hypothalamus, hippocampus, and brainstem, as well as in peripheral tissues such as the gastrointestinal tract. It functions as an autoreceptor to inhibit the release of NPY and modulates appetite suppression, energy homeostasis, and gastrointestinal motility. NPY2R couples to Gi/o proteins, reducing adenylate cyclase activity, cAMP levels, and neurotransmitter release. Activation of NPY2R reduces food intake and promotes energy expenditure, making it a key target for anti-obesity therapies. It also plays roles in neuroprotection, stress regulation, and cardiovascular function. Dysregulation of NPY2R signaling is associated with metabolic disorders, anxiety, and inflammatory conditions. NPY2R agonists are being developed to treat obesity by enhancing satiety and energy expenditure, highlighting its role as a critical regulator of feeding behavior and metabolism.