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Drug transporters encoded by solute carrier (SLC) family are distributed in multiple organs including kidney, liver, placenta, brain, and intestine, where they mediate the absorption, distribution, and excretion of a diverse array of environmental toxins and clinically important drugs. Alterations in the expression and function of these transporters play important roles in intra- and inter-individual variability of the therapeutic efficacy and the toxicity of many drugs. Consequently, the activity of these transporters must be highly regulated to carry out their normal functions. While it is clear that the regulation of these transporters tightly depends on genetic mechanisms, many studies have demonstrated that these transporters are the target of various post-translational modifications. This review article summarizes the recent advances in identifying the posttranslational modifications underlying the regulation of the drug transporters of SLC family. Such mechanisms are pivotal not only in physiological conditions, but also in diseases.