CH25H (cholesterol 25-hydroxylase) catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25-HC), a bioactive oxysterol that serves dual roles in lipid homeostasis and immune regulation. The enzyme represses cholesterol biosynthetic enzymes by blocking sterol regulatory element-binding protein (SREBP) processing, thereby preventing excessive cholesterol accumulation. 25-HC is an intermediate in the synthesis of 7α,25-dihydroxycholesterol, which acts as a ligand for the chemotactic receptor GPR183/EBI2, directing lymphocyte positioning in lymphoid tissues and inflamed tissues 1. As an interferon-stimulated gene, CH25H mediates antiviral immunity against enveloped viruses including SARS-CoV-2 by promoting cholesterol internalization and restricting viral membrane fusion. In macrophages, CH25H prevents inflammasome activation by maintaining mitochondrial integrity and protecting against cholesterol-dependent mitochondrial DNA release 2. However, recent evidence suggests context-dependent roles: macrophage-derived 25-HC amplifies inflammatory responses in atherosclerosis by modifying plasma membrane cholesterol accessibility and enhancing Toll-like receptor signaling 3, while in tumors, CH25H expression in immunosuppressive macrophage subsets restrains anti-tumor immunity through metabolic reprogramming via AMPKα activation 4. In neuroinflammation, CH25H/25-HC potentiates tau-mediated neurodegeneration in Alzheimer's disease models 5. CH25H emerges as both a therapeutic target and biomarker across inflammatory diseases ranging from asthma to viral infection to cancer 6.