PT - JOURNAL ARTICLE AU - Sydney Stern AU - Ritika Kurian AU - Hongbing Wang TI - Clinical relevance of the constitutive androstane receptor AID - 10.1124/dmd.121.000483 DP - 2022 Jan 01 TA - Drug Metabolism and Disposition PG - DMD-MR-2021-000483 4099 - http://dmd.aspetjournals.org/content/early/2022/02/27/dmd.121.000483.short 4100 - http://dmd.aspetjournals.org/content/early/2022/02/27/dmd.121.000483.full AB - Constitutive androstane receptor (CAR, NR1I3), a xenobiotic receptor, has long been considered a master mediator of drug disposition and detoxification. Accumulating evidence indicates that CAR also participates in various physiological and pathophysiological pathways regulating the homeostasis of glucose, lipid, and bile acids, and contributes to cell proliferation, tissue regeneration and repair, as well as cancer development. The expression and activity of CAR can be regulated by various factors including small molecular modulators, CAR interaction with other transcription factors, and naturally occurring genetic variants. Given that the influence of CAR has extended beyond the realm of drug metabolism and disposition and has expanded into a potential modulator of human diseases, growing efforts have centered around understanding its clinical relevance and impact on human pathophysiology. This review highlights the current information available regarding the contribution of CAR to various metabolic disorders and cancers and ponders the possible challenges that might arise from pursuing CAR as a potential therapeutic target for these diseases.Significance Statement <>The growing importance of CAR in glucose and lipid metabolism as well as its potential implication in cell proliferation emphasizes a need to keenly understand the biological function and clinical impact of CAR. This minireview captures the clinical relevance of CAR by highlighting its role in metabolic disorders and cancer development.