The liver X receptor alpha (LXR alpha) is a nuclear hormone receptor and can function as a ligand inducible transcription factor capable of acting as a co-repressor and/or co-activator for gene expression. Nuclear receptors contain a series of conserved domains or regions. These domains/regions include a variable NH2-domain (A/B region), a conserved DNA-binding domain (DBD or region C), a linker region (also called a hinge region) (region D), a ligand binding domain (LBD or region E), and in some receptors a variable COOH-terminal (region F). LXR alpha forms a heterodimer with RXR to activate transcription, and is a member of class II, which encompass receptors that are mainly (not always) localized in the nucleus even when not bound by ligand. (Class I nuclear receptors such as the steroid hormone receptors are sequestered in the cytoplasm and migrate to the nucleus upon ligand binding.) Unliganded LXR alpha interacts with co-repressors and represses transcription. When ligand is bound, the receptor undergoes conformational changes, leading to a decrease in the interaction with corepressors and an increase in interactions with co-activators such as SRC-1 and GRIP-1, which then leads to transcriptional activation. The specificity of the co-activator interaction is determined by the particular ligand that is bound. LXRs are expressed in a wide variety of tissues. The alpha isoform controls fatty acid synthesis and is expressed in metabolically active tissues such as the liver, kidney, adipose tissue, macrophages, and intestine. The beta isoform is ubiquitiously expressed, and controls highdensity lipoprotein assembly through its control of ABCA1 expression. Synthetic LXR agonists which are not subtype-specific have been developed. Mice treated with these agonists show a decrease in atherosclerosis, but unfortunately also show an increase in fatty acid synthesis leading to triglyceride accumulation. It is believed that subtype-selective agonists might allow dissociation of the favorable cholesterol effects from the unfavorable triglyceride effects.