HPGDS (hematopoietic prostaglandin D synthase) is a bifunctional cytosolic enzyme that primarily catalyzes the glutathione-dependent conversion of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2), while also possessing glutathione S-transferase activity 1. The enzyme is expressed predominantly in immune cells including mast cells, antigen-presenting cells, Th2 cells, and macrophages 12. HPGDS plays critical roles in inflammatory regulation through PGD2 production, which mediates vasodilatation, bronchoconstriction, and platelet aggregation inhibition 1. In macrophages, HPGDS maintains protumoral phenotypes through PGD2 autocrine signaling via DP1/DP2 receptors and inhibits CD8+ T-cell function, contributing to immunotherapy resistance 3. The enzyme demonstrates protective effects in pulmonary arterial hypertension by reducing vascular remodeling 2 and promotes wound healing in diabetes by enhancing anti-inflammatory responses 4. However, HPGDS also contributes to pathological processes, including diabetic nephropathy progression through pyroptosis activation 5. Altered HPGDS levels serve as biomarkers in multiple diseases, including decreased levels in childhood asthma 6, lupus nephritis 7, and as early predictors of Parkinson's disease 8, highlighting its clinical significance across diverse pathological conditions.