Cholesterol levels are sensed by two distinct transcription factor pathways: the sterol regulatory element-binding proteins (SREBPs) and the liver X receptors (LXRs).The LXRs — namely LXRα and LXRβ — are sterolactivated transcription factors that are regulated by the binding of physiological ligands, such as oxysterols, and certain intermediates in the cholesterol biosynthetic pathway, such as desmosterol. Interestingly, most endogenous sterols that activate LXRs can also inhibit the activation of the SREBP pathway, which underscores that the LXR and SREBP pathways are highly interconnected in control of cholesterol homeostasis. The two LXR isotypes share substantial sequence identity and possess a domain structure that is common to most nuclear receptors.
 The transcriptional activity of LXRs is dependent on the formation of heterodimers with retinoid X receptors (RXRs). Upon agonist binding, the conformation of the LXR–RXR complex is altered, leading to the release of nuclear receptor co-repressors such as silencing mediator of retinoic acid and thyroid hormone receptor (SMRT; also known as NCOR2) and NCOR1, and the recruitment of nuclear receptor co-activators such as E1A-associated protein p300 (EP300) and activating signal co-integrator 2 (ASC2; also known as NCOA6). LXRs have a physiological role in sterol homeostasis.Several direct LXR target genes are intimately linked to reverse cholesterol transport, a process by which excess cholesterol from peripheral tissues is returned to the liver by high-density lipoprotein (HDL) for ultimate excretion in bile.  LXRs also induce the expression of a cadre of apolipoproteins that may serve as cholesterol acceptors, including APOE, APOC1, APOC2 and APOC4. 
LXRs regulate the expression of a series of lipoproteinremodelling enzymes, including phospholipid transfer protein (PLTP), lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP), which are collectively postulated to modify lipoproteins in a way that facilitates the uptake of excess cholesterol from the periphery and its transfer back to the liver for excretion. As a ligand-activated nuclear receptor, LXR is also a potentially attractive drug target, and manipulating the LXR pathway may complement the effects of statins. LXR ligands have entered early-stage clinical trials for the potential treatment of atherosclerosis and hyperlipidaemia. Moreover, new roles for LXR signalling in physiology and disease continue to emerge and so this remains an active area of investigation.

References

1.Hong C, Tontonoz P. Nat Rev Drug Discov. 2014;13(6):433–444.