NR1I3 mediates the induction of transcription of cytochrome P450 (CYP) genes by phenobarbital (PB) and PB-type inducers. NR1I3 activation induces hepatic expression of detoxification enzymes and transporters and increases liver size. NR1I3 can also regulate both liver homeostasis and tumorigenesis in response to xenobiotic stresses.