CH25H (cholesterol 25-hydroxylase) catalyzes the conversion of cholesterol to 25-hydroxycholesterol (25-HC), a bioactive oxysterol with pleiotropic functions 1. In lipid metabolism, 25-HC represses cholesterol biosynthetic enzymes by blocking sterol regulatory element binding protein (SREBP) processing 1. CH25H plays a critical role in lymphoid cell positioning through 25-HC serving as a ligand for the G protein-coupled receptor GPR183/EBI2, enabling lymphocyte recruitment to inflamed lymph nodes and tissues 2. As an interferon-stimulated gene, CH25H exhibits broad antiviral activity; its product restricts SARS-CoV-2 replication by activating the ER enzyme ACAT to internalize plasma membrane cholesterol and inhibit viral S protein-mediated membrane fusion 34. In macrophages, 25-HC prevents inflammasome activation by maintaining mitochondrial integrity and restraining cholesterol accumulation, thereby blocking AIM2 inflammasome-mediated IL-1β release 5. However, context-dependent roles exist: macrophage-derived 25-HC amplifies atherosclerotic inflammation and plaque instability 6, while in tumors, CH25H expression in macrophages promotes immunosuppressive phenotypes that impair anti-tumor immunity, establishing CH25H as an immunometabolic checkpoint 7. CH25H is elevated in asthma and tauopathy-associated neuroinflammation 89, highlighting disease relevance. Clinically, CH25H emerges as a therapeutic target for modulating immune responses across inflammatory, infectious, and malignant diseases.