Ch25h, or cholesterol 25-hydroxylase, is a crucial enzyme that converts cholesterol to 25-hydroxycholesterol (25HC), playing a significant role in cholesterol metabolism, inflammation, and immune responses [1,2,4,7,8,9]. It is involved in various biological pathways such as those related to lipid metabolism, innate and adaptive immune responses, and is associated with numerous disease conditions including cancer, osteoarthritis, and ischemic stroke [1,2,3,4,5,6,7,8]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, Ch25h deficiency in chondrocytes was found to abrogate the pathogenesis of osteoarthritis, indicating its role in the CH25H-CYP7B1-RORα axis regulating osteoarthritis [2]. In microglia, Ch25h-/-mice had significantly increased infarct volume following ischemic stroke compared to Ch25h + / +, suggesting the neuroprotective role of CH25H + microglia subcluster [3]. In lung adenocarcinoma, low expression of CH25H in leukocytes was associated with metastasis, and its reduced expression in lung adenocarcinoma patients was linked to a higher disease stage and worse prognosis [6]. In liver, Ch25h-/-mice on a high-fat diet showed higher serum cholesterol and triglyceride levels and were prone to hepatic steatosis, demonstrating its role in preventing liver steatosis [8].

In conclusion, Ch25h has essential functions in lipid metabolism, immune responses, and inflammation. Model-based research, particularly using KO mouse models, has revealed its significance in diseases like osteoarthritis, ischemic stroke, lung adenocarcinoma, and liver steatosis. Understanding Ch25h provides insights into disease mechanisms and potential therapeutic targets.