Ptges2, also known as microsomal prostaglandin E synthase-2 (mPGES-2), is an enzyme involved in the synthesis of prostaglandin E2 (PGE2) from COX-derived PGH2 [5]. It can also metabolize PGH2 to malondialdehyde by forming a complex with heme. Ptges2 is associated with multiple biological pathways and is of great biological importance in processes such as systemic insulin sensitivity regulation, lipid metabolism, and inflammation-related responses [2,4]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In AKI (acute kidney injury) models, both global and tubule-specific Ptges2-deficient mice treated with cisplatin or subjected to unilateral renal ischemia/reperfusion showed decreased renal dysfunction and morphological damage. Mechanistically, Ptges2 deficiency inhibited ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis, indicating that blocking Ptges2 may be a promising therapeutic strategy for AKI [3]. In the context of diabetic kidney disease (DKD), global knockout or pharmacological blockage of Ptges2 attenuated diabetic podocyte injury, tubulointerstitial fibrosis, lipid accumulation, and lipotoxicity. The mechanism involves the competition between Ptges2 and Rev-Erbα for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney, suggesting a potential treatment strategy for DKD through Ptges2 inhibition [4].

In conclusion, Ptges2 is a key enzyme in PGE2 synthesis and is involved in important biological processes. Studies using KO/CKO mouse models have revealed its role in AKI and DKD, providing potential therapeutic directions for these diseases. Additionally, it may be associated with other conditions such as basal cell carcinoma, as it was identified as a potential biomarker and therapeutic target for BCC through proteome-wide mendelian randomization, colocalization, and MR-PheWAS analyses [1].