Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease

Drug transporters are crucial for facilitating the distribution and elimination of drugs from the body, yet their broader physiological functions remain underexplored. Beyond drug handling, these transporters regulate key biological processes, including barrier integrity, metabolic homeostasis, detoxification, and immune response. Here we examine the endogenous roles of representative drug transporters along with their involvement in disease pathophysiology, particularly in neurological disorders, cancer, metabolic syndromes, kidney disease, and hepatic disorders. Given the complex interplay between transporters and various physiological processes, a comprehensive understanding of their roles beyond drug transport is imperative for advancing therapeutic strategies and fully grasping their impact on human health. By elucidating their mechanistic roles, researchers can refine drug development and identify novel therapeutic targets. This review underscores the need for continued research into transporters' diverse functions and their potential as key modulators in disease prevention and treatment.