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Acyl-CoA:cholesterol acyltransferase 1 (ACAT1 or SOAT1) is an integral membrane enzyme predominantly localized in the endoplasmic reticulum, where it catalyzes the conversion of free cholesterol and long-chain fatty acyl-CoA into cholesteryl esters for intracellular storage or lipoprotein assembly[3][5][7]. ACAT1 is ubiquitously expressed in nearly all mammalian tissues and plays a key role in maintaining cholesterol homeostasis, preventing toxic accumulation of free cholesterol within cells[7]. Dysregulation or increased activity of ACAT1 is implicated in atherosclerosis, where it drives foam cell formation in macrophages, and in multiple cancers, where it sustains high levels of cholesteryl esters supporting tumor growth[4]. Recent research has also implicated ACAT1 as a therapeutic target for Alzheimer's disease and viral infections such as hepatitis B, where targeting this enzyme may restore immune function and improve disease outcomes[2][4][6][8]. While ACAT1 inhibitors are under investigation, their therapeutic use is complicated by tissue- and context-specific effects and potential safety concerns with systemic inhibition[2][4].
Inhibition of cholesterol esterification by blocking the conversion of cholesterol to cholesteryl esters[4][6] Modulation of lipid metabolism, limiting storage of cholesterol esters and affecting formation of lipoproteins[3][5][7] Potential restoration of immune cell function in cancer and viral infections through metabolic reprogramming[8]
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