PTGES (prostaglandin E synthase) is the terminal enzyme in the COX-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway, catalyzing the glutathione-dependent conversion of prostaglandin H2 to PGE2 in response to inflammatory stimuli 1. Beyond this core catalytic function, PTGES exhibits additional enzymatic activities including glutathione transferase and peroxidase functions 1. Mechanistically, PTGES promotes myofibroblast differentiation through AKT-mediated activation of the HIF-1α-dependent glycolysis pathway 2. In cancer contexts, PTGES expression correlates with metabolic reprogramming, epithelial-mesenchymal transition, and immune suppression, particularly through downregulation of MHC pathways and reduced CD8+ T cell activation 3. PTGES is also induced as part of the inflammatory response in monocytic cells following LPS and interferon-gamma stimulation 4. Clinically, PTGES emerges as a biomarker in multiple disease contexts. In lung fibrosis, PTGES upregulation contributes to pathological myofibroblast differentiation 2. In pancreatic ductal adenocarcinoma, elevated PTGES expression associates with worse prognosis and correlates with driver gene mutations including TP53 and KRAS 3. PTGES is also implicated in intervertebral disc degeneration-associated pain and inflammation 5. Additionally, PTGES functions in immune evasion within prostate cancer microenvironments through IRF1-mediated transcriptional regulation 6.