DHCR24, also known as 3β-hydroxysterol-Δ24 reductase, is a key enzyme in cholesterol synthesis. It catalyzes the conversion of desmosterol to cholesterol, thereby playing a crucial role in maintaining cholesterol homeostasis. Cholesterol is essential for providing structural components to cells and can be transformed into various active substances to regulate cell signaling pathways. The gene is involved in multiple biological processes and diseases, making genetic models valuable for its study [2,3,5].

In a well-established mouse model (APOE*3-Leiden.CETP mice), inhibition of DHCR24 by SH42 increased desmosterol levels in the liver and plasma, reduced hepatic lipid content and steatosis, decreased plasma fatty acid and cholesteryl ester concentrations, and alleviated liver inflammation by preventing Kupffer cell activation and monocyte infiltration. These beneficial effects were strictly LXRα-dependent and did not cause hyperlipidemia [1]. In endothelium-specific DHCR24 knockout mice, there was increased endothelial cell senescence, characterized by increased P16 and senescence-associated secretory phenotype, decreased SIRT1 and cell proliferation, impaired endothelium-dependent relaxation, and elevated blood pressure [4].

In conclusion, DHCR24 is essential for maintaining cholesterol homeostasis and is involved in multiple biological processes. Studies using gene knockout mouse models have revealed its role in diseases such as non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) and endothelial cell senescence. Understanding DHCR24 function through these models provides potential therapeutic strategies for related diseases.