NR1H3 encodes liver X receptor alpha (LXRα), a nuclear receptor that functions as a ligand-dependent transcriptional activator critical for lipid metabolism and immune regulation 1. The receptor heterodimerizes with retinoid X receptor (RXR) to regulate target genes through LXRE response elements, playing essential roles in cholesterol homeostasis by controlling cholesterol uptake and transport 1. NR1H3 exhibits tissue-specific expression patterns and regulates osteogenic differentiation through endoplasmic reticulum stress pathways, as demonstrated in calcific aortic valve disease where reduced NR1H3 expression exacerbates calcification 2. The receptor shows functional cross-talk with RORα in regulating metabolic genes, with mutual suppression affecting hepatic triglyceride accumulation 3. In immune contexts, NR1H3 is highly expressed in pro-inflammatory M1-like macrophages and serves as a prognostic biomarker in diffuse large B-cell lymphoma, where high expression correlates with improved survival 4. Disease associations include multiple sclerosis risk through genetic variants that regulate NR1H3 expression 5, vitiligo susceptibility 6, and tuberculosis pathogenesis where decreased expression affects cholesterol homeostasis critical for mycobacterial survival 7. Therapeutically, NR1H3 pathway activation shows protective effects in septic myocardial injury 8.