Neuropeptide Y4 receptor (Y4 receptor (sometimes abbreviated as NPY4R))

The **neuropeptide Y4 receptor (Y4 receptor, NPY4R)** is a member of the G protein-coupled receptor (GPCR) superfamily, specifically within the neuropeptide Y (NPY) receptor family[4][5]. It is notable for its high affinity and selectivity for the endogenous ligand **pancreatic polypeptide (PP)**, which is secreted by the pancreas following food ingestion[3][5][7]. The Y4 receptor is primarily expressed in the gastrointestinal tract, pancreas, central nervous system (including hypothalamus and hippocampus), and other tissues[4]. Functionally, the Y4 receptor mediates satiety signals—its activation suppresses appetite and food intake, and it is a pivotal regulator of energy balance[5]. These characteristics make it a promising therapeutic target for metabolic diseases such as obesity, as well as a potential biomarker and drug target in certain types of cancer where the receptor is overexpressed[4][5]. Both peptide-derived and small-molecule Y4-specific agonists and allosteric modulators have been developed as experimental and investigational drugs, some progressing to clinical trial evaluation for obesity management[5][6]. The receptor's structure has been elucidated primarily via computational modeling and mutagenesis, revealing key transmembrane domains necessary for ligand binding and signal transduction[1][6]. Safety considerations focus on the risk of overly suppressing appetite (leading to anorexia) and possible CNS or off-target effects due to the widespread, though typically low-level, tissue expression of the receptor[4][5].

Other names

Pancreatic polypeptide Y4 receptorNeuropeptide Y receptor Y4NPY Y4 receptorNPY4R

Agonists: activate Y4 receptor to mimic or enhance satiety and reduce food intake; Antagonists: block receptor-mediated signaling, though clinical use mostly focuses on agonists for obesity and related disorders[5][6]