PTGES3 (prostaglandin E synthase 3) is a cytosolic enzyme catalyzing conversion of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) 1, with activity regulated through association with hsp90 2. Beyond its classical enzymatic role, PTGES3 functions as a molecular chaperone that disrupts transcriptional activation by promoting disassembly of regulatory complexes 34, and facilitates HIF-alpha protein hydroxylation via EGLN1/PHD2 interaction 5. Clinically, PTGES3 demonstrates significant disease relevance across multiple cancers. In glioblastoma, elevated PTGES3 expression and resulting PGE2 production induce neuronal senescence, promoting tumor survival after radio-/chemotherapy; PTGES3 knockdown reduces neuronal senescence and delays tumor progression 6. In prostate cancer, PTGES3 directly binds androgen receptor (AR), regulates AR protein stability, and is necessary for AR function at target genes; PTGES3 expression correlates with AR-directed therapy resistance 7. In lung adenocarcinoma, elevated PTGES3 correlates with advanced stage, poor prognosis, and participates in immune regulation networks 89. PTGES3 is also highly expressed in hepatocellular carcinoma and represents a therapeutic target amenable to PROTAC-mediated degradation 10. In rheumatoid arthritis, PTGES3 serves as the primary regulator of arachidonic acid metabolism, with modulation improving lipid homeostasis and reducing inflammation 11. Additionally, PTGES3/PTGER4 signaling suppresses fetal T cell activation during immune system maturation 12. These diverse functions establish PTGES3 as a pleiotropic therapeutic target.