Pancreatic polypeptide receptor Y4 (Y4 receptor)

Pancreatic polypeptide receptor Y4 is a G protein-coupled receptor (GPCR) primarily recognized for binding pancreatic polypeptide (PP) with high affinity, as well as peptide YY and neuropeptide Y to a lesser degree. The receptor is structurally typical of class A GPCRs, featuring seven transmembrane domains. It is encoded by the NPY4R or PPYR1 gene and is highly expressed in the brainstem, hypothalamus, pancreas, and gut, playing a central role in regulating appetite and energy homeostasis by transducing satiety signals in response to food intake. Overexpression of Y4 receptor has been identified in certain cancers (e.g., adenocarcinoma), and dysregulation of this receptor-ligand axis is associated with both metabolic disease (obesity, diabetes) and pancreatic endocrine tumors. Both endogenous ligands (PP, PYY, NPY) and investigational drugs (e.g., Obinepitide, UR-AK86c, VU0506013) act via this receptor, making it a therapeutic target for obesity and metabolic syndromes. Key safety concerns include the risks associated with appetite suppression and broad expression effects.

Other names

Neuropeptide Y receptor type 4PPYR1NPY4RY4 receptor

Agonists mimic or enhance pancreatic polypeptide-mediated activation, reducing appetite and energy intake Antagonists or allosteric modulators may inhibit or alter receptor activity, affecting appetite and metabolic balance