Systemic exposure of a drug is determined by the pharmacokinetic (PK) properties including absorption, distribution, metabolism, and elimination (ADME). Often, an efficacious drug relies on adequate drug levels distributed to the target tissues for a desired period of time to regulate the pathway of disease. 1 Over the last two decades, pharmaceutical industries have been focusing to develop in vitro tools using hepatocytes or liver microsome to select the compounds that are metabolically stable and have optimal half-lives to fit at least once a day dosing regimen. Surprisingly, metabolic stable compounds often result in unpredictable drug elimination in vivo, due to the involvement of drug transporters. While drug clearance via CYP P450 metabolizing enzymes have been well-characterized, 2 membrane transporters involve in drug pharmacokinetics and disposition are increasingly scrutinized for their contribution to the suboptimal PK and organ distribution and the undesired safety or efficacy outcomes. As a result, the impact of transporters on patient safety and efficacy become critical considerations in drug discovery and development, mainly to assess drug distribution to the target or off-target organs and to minimize the potential drug-drug interactions (DDIs).