Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway (PubMed:10869354, PubMed:11795891). Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:11795891, PubMed:10869354). Plays a key role in inflammation response, fever and pain (PubMed:12835414, PubMed:14566340). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2. In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (By similarity). prostaglandin H2 = prostaglandin E2 2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin E2 prostaglandin G2 = (15S)-15-hydroperoxy-prostaglandin E2 1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-S-glutathione + chloride + H(+) (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2 glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + glutathione disulfide + H2O Activity is increased markedly in macrophages and osteoblasts following pro-inflammatory stimuli. Optimum pH is 8. Lipid metabolism; prostaglandin biosynthesis. Homotrimer. Colocalizes with PTGS1/COX-1 and PTGS2/COX-2 in the perinuclear compartment. Induced by pro-inflammatory stimuli and down-regulated by anti-inflammatory glucocorticoid. Deficient mice are viable and fertile and develop normally (PubMed:12835414, PubMed:14566340). However mice display a marked reduction in inflammatory responses and reduced pain sensitivity (PubMed:12835414). PTGES deletion results in a reduction of PGE2 levels in the central nervous system in association with the impaired LPS-induced febrile response (PubMed:14566340). Belongs to the MAPEG family.