Regulation of cholesterol homeostasis by SREBP2 and LXR. (A) In conditions of low cholesterol levels, SCAP escorts SREBP2 to Golgi apparatus, where it is cleaved and activated. Subsequently, SREBP2 binds and activates the expression of genes regulating de novo cholesterol synthesis. LXRs remain in a repressive state. (B) In conditions of high cholesterol levels, oxysterols, cholesterol, or desmosterol keeps the trimolecular complex INSIG/SCAP/SREBP2 in the ER, not allowing cholesterol synthesis. Oxysterols engage LXRs, which activate expression of the cholesterol transporters ABCA1 and ABCG1. These transporters induce the reverse cholesterol transport pathway, leading to elimination of excess cholesterol through bile acid formation and excretion.