 Using several approaches, including efflux assays, immunoprecipitation/-blotting/-histochemistry, paracellular permeability assay, fluorescence activated cell sorting, cytokine assay, and immunofluorescence microscopy, recent studies suggest that obese individuals have compromised intestinal BCRP functions and that diet-induced obese mice recapitulate these outcomes.It was also demonstrated that the compromised BCRP functions during obesity were due to loss of Janus kinase 3 (JAK3)-mediated tyrosine phosphorylation of BCRP.Results in the studies indicated that JAK3-mediated phosphorylation of BCRP promotes its interactions with membrane-localized β-catenin essential not only for BCRP expression and surface localization, but also for the maintenance of BCRP-mediated intestinal drug efflux and barrier functions.