Cholesterol 25-hydroxylase (CH25H)

Cholesterol 25-hydroxylase (CH25H) is an interferon-inducible, non-cytochrome P450 enzyme localized mainly in the endoplasmic reticulum that catalyzes the hydroxylation of cholesterol to generate 25-hydroxycholesterol (25-HC), an oxysterol with wide-ranging effects on lipid metabolism and immune function. CH25H expression is abundant in macrophages, the liver, and immune tissues, where it is upregulated by stimuli such as interferons and TLR ligands. Through its product, 25-HC, CH25H can inhibit cholesterol biosynthesis (by blocking SREBP2 activity), shape immune responses (by suppressing T cell proliferation and modulating cytokine production), act as a negative regulator of cell growth during immune activation, and confer broad-spectrum antiviral properties by preventing viral entry through membrane fusion. CH25H and 25-HC play roles in both limiting excessive inflammation (as in autoimmunity and colitis) and mediating host defense against pathogens, but their effects depend on cellular and disease context. No approved drugs directly target CH25H, but its regulatory axis is being investigated for therapeutic potential in infection, inflammation, and cholesterol-related disorders.

Other names

Cholesterol 25-monooxygenaseC25Hcholesterol 25-hydroxylasecholesterol 25-monooxygenaseh25OH

Inhibition of cholesterol biosynthesis through suppression of SREBP2 activity by its product, 25-hydroxycholesterol (25-HC). Modulation of immune cell differentiation and activity (e.g., suppression of T cell proliferation, modulation of Th17 differentiation, regulation of inflammasome activity). Antiviral mechanism by blockade of viral–cell membrane fusion by 25-HC.