Liver X receptors NR1H3 (LXR alpha) and NR1H2 (LXR beta) are sterol-responsive transcription factors that become activated upon the engagement with their cognate oxysterol ligands. Ligand-activated NR1H2 & NR1H3 induce a genetic program aimed at reducing the cellular sterol load by limiting cholesterol uptake, attenuating cholesterol biosynthesis and promoting cholesterol efflux. This Reactome module describes the NR1H2 & NR1H3-regulated expression of MYLIP (IDOL) gene, an E3 ubiquitin ligase, that triggers ubiquitination of the low-density lipoprotein receptor (LDLR) on its cytoplasmic domain, targeting it for degradation and thereby limiting cholesterol uptake (Zelcer N et al. 2009; Zhang L et al. 2012).