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Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post\u2010translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of\n                    <jats:italic>in vitro<\/jats:italic>\n                    observations to\n                    <jats:italic>in vivo<\/jats:italic>\n                    outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation\u2010mediated changes in transporter function on drug disposition and response.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2605","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T14:24:35Z","timestamp":1649341475000},"page":"461-484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Regulation of Drug Transport Proteins\u2014From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-4929","authenticated-orcid":false,"given":"Kim L.R.","family":"Brouwer","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Evers","sequence":"additional","affiliation":[{"name":"Preclinical Sciences and Translational Safety Johnson &amp; Johnson, Janssen Pharmaceuticals  Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-3557","authenticated-orcid":false,"given":"Elizabeth","family":"Hayden","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-7734","authenticated-orcid":false,"given":"Shuiying","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy Yanfei","family":"Li","sequence":"additional","affiliation":[{"name":"PKDM Amgen Inc.  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