PTGER4 (prostaglandin E receptor 4) is a G-protein coupled receptor that mediates prostaglandin E2 (PGE2) signaling through adenylate cyclase activation 1. The receptor plays critical roles in intestinal homeostasis and immune regulation. In intestinal epithelial cells, PTGER4 activation suppresses necroptosis and promotes resolution of colitis, with EP4 expression correlating with improved inflammatory bowel disease outcomes 2. PTGER4-expressing intestinal macrophages drive mucosal healing by secreting CXCL1 via MAPK signaling, supporting epithelial regeneration during intestinal inflammation 3. During tumorigenesis, PTGER4 signaling promotes stem cell expansion through PGE2-induced YAP dephosphorylation and nuclear translocation, facilitating colorectal cancer initiation 1. In tumor microenvironments, PGE2-PTGER4 signaling impairs CD8+ T cell and macrophage immunity by downregulating metabolic pathways including oxidative phosphorylation and glycolysis 4. PTGER4 also mediates tumor cell-macrophage cross-talk in liver cancer 5. Additionally, PTGER4 participates in fetal immune tolerance mechanisms 6, and genetic variation upstream of PTGER4 associates with perianal fistula susceptibility in Crohn's disease 7. These findings establish PTGER4 as a pleiotropic regulator controlling epithelial repair, immune homeostasis, and cancer pathogenesis through PGE2 signaling.