NR1I2 (pregnane X receptor, PXR) is a ligand-activated nuclear transcription factor that serves as a critical xenobiotic sensor regulating drug metabolism and detoxification pathways 1. Upon activation by diverse ligands including xenobiotics and endogenous compounds, NR1I2 translocates to the nucleus and regulates transcription of major drug-metabolizing enzymes and transporters, facilitating xenobiotic elimination 1. Beyond xenobiotic metabolism, NR1I2 plays important roles in maintaining gastrointestinal barrier function, where microbial metabolites like indole 3-propionic acid activate PXR to regulate intestinal barrier integrity through modulation of TNF-α and junctional proteins, with PXR-deficient mice showing increased gut permeability 2. NR1I2 also demonstrates protective vascular functions, as PXR activation suppresses abdominal aortic aneurysm formation by inhibiting oxidative stress through the GABRA3-ROS-JNK pathway 3. Genetic polymorphisms in NR1I2 have been studied for associations with drug-induced hepatotoxicity and disease susceptibility, though meta-analyses show inconsistent results for anti-tuberculosis drug-induced hepatotoxicity 4 and inflammatory bowel disease risk 5. However, specific NR1I2 variants like rs7643645 have been associated with HIV progression to AIDS 6, and rs3814055 may contribute to anti-tuberculosis drug hepatotoxicity risk 7.