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Liver X receptors (LXRs) are nuclear receptors that act as metabolic sensors for cellular cholesterol (Xol) and oxysterol content. Increased oxysterol levels activate LXRs, which then induce: the removal of cholesterol out of peripheral cells; transport of this cholesterol to the liver; excretion of cholesterol through production of bile acids; and inhibition of intestinal cholesterol absorption. Recent evidence indicates that LXRs are not only master regulators of cholesterol homeostasis, but also decrease the development of atherosclerosis - a disease intimately linked with abnormal cholesterol homeostasis. This evidence shows that LXRs are promising drug development targets for atherosclerosis.