DHRS9 (dehydrogenase/reductase 9) is a microsomal enzyme that functions as a broad-spectrum oxylipin dehydrogenase with significant roles in lipid metabolism and inflammatory regulation. The enzyme exhibits robust oxidative activity toward various bioactive oxylipins, including hydroxylated octadecanoids, eicosanoids, and docosanoids, as well as inflammatory mediators like Leukotriene B4 and proresolving mediators such as Resolvin D1 and Lipoxin A4 1. DHRS9 operates through NAD+-dependent oxidation, with a large substrate binding cavity accommodating diverse oxygenated hydrocarbons of 18-22 carbons 2. The enzyme plays a crucial role in terminating inflammatory responses by metabolizing bioactive lipid mediators 1. Disease relevance includes its function as a tumor suppressor, where reduced DHRS9 expression correlates with poor prognosis in oral squamous cell carcinoma and promotes colon cancer progression through effects on oxidative phosphorylation 34. Naturally occurring mutations (S202L and D286H) linked to early-onset epilepsy significantly impair enzyme functionality 2. Clinically, DHRS9 serves as a stable marker for human regulatory macrophages and shows promise as a diagnostic marker in various pathological conditions 5.