Gastrin-releasing peptide (GRP) is a neuropeptide hormone that functions as a signaling molecule through activation of the GRP receptor (GRPR), a G protein-coupled receptor widely distributed in the gastrointestinal tract and central nervous system 1. GRP binding to GRPR activates phospholipase C signaling and triggers receptor internalization through arrestin-dependent mechanisms, with distinct trafficking routes involving arrestin2 and arrestin3 2. In normal physiology, GRP expression is limited primarily to gastric antral epithelial cells 3 and plays crucial roles in male sexual function, including spinal control of erections and ejaculation 4. Clinically, GRP/GRPR signaling is implicated in multiple pathological conditions. GRP stimulates growth of renal and prostate cancer cells and represents a key neuroendocrine peptide in advanced prostate cancer progression 4. Additionally, GRP/GRPR activation enhances alcohol-associated liver injury through IRF1-mediated Caspase-1 inflammasome activation and NOX2-dependent reactive oxygen species generation 5. Aberrantly expressed GRP receptors on gastrointestinal cancers exhibit altered pharmacology compared to normal tissue 3. These findings support the therapeutic potential of GRPR antagonists for treating inflammation-associated diseases and cancer, with selective human GRPR antagonists identified for clinical investigation 15.