NR1H2 (LXRβ) is a ligand-dependent nuclear receptor that functions as a cholesterol sensor, regulating lipid homeostasis and metabolism 1. The receptor binds DNA at DR-4 elements and activates transcription in response to oxysterol binding 2. NR1H2 controls cholesterol uptake by regulating MYLIP-dependent ubiquitination of lipoprotein receptors (LDLR, VLDLR, LRP8) [UniProt], and coordinates LPCAT3-dependent phospholipid remodeling in hepatocyte endoplasmic reticulum membranes to promote SREBF1 processing and lipogenesis. The receptor also suppresses hepatic inflammation during acute phase responses by preventing N-Cor corepressor complex dissociation 3. NR1H2 demonstrates critical roles beyond lipid metabolism: it regulates pancreatic β-cell insulin secretion, with genetic variants associated with impaired insulin secretion in type 2 diabetes risk populations 4. The receptor controls pluripotency programming, where Nr1h2 activation alone rewires embryonic stem cells into expanded pluripotent states enabling enhanced blastoid formation and implantation capacity 5. NR1H2 variants associate with preeclampsia risk through effects on trophoblast invasion and endoglin regulation 6. Mediterranean diet interventions upregulate NR1H2 expression alongside other cholesterol efflux genes in cardiovascular high-risk patients 7, suggesting therapeutic potential for cardiovascular protection through dietary modulation of NR1H2 activity.