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The organic anion transporters (OATs) are a subclass of the large SLC22 family of transmembrane proteins, which mediate the transport of a wide variety of endogenous metabolites, signaling molecules, and exogenous compounds including potential cytotoxic drugs and toxins. These transporters are expressed in a range of tissues including brain, retina, placenta, testes, olfactory mucosa, liver, intestine, and kidney. Together with Phase I and Phase II metabolizing enzymes, the OATs play a role in the cellular uptake, biotransformation, and clearance of the physiological and toxic compounds, many of which are excreted by the kidney. Although much of the original work in the field was based on in vitro data, in recent years a number of studies in Oat knockout mice, as well as analysis of the consequences of human SNPs, have cemented this view. Systems biology approaches applied to knockout mice metabolomics and transcriptomics data suggest a broader role for OATs in metabolism and signaling, including communication occurring between organs. This view is more fully expressed in the Remote Sensing and Signaling Theory, which may be relevant to both SLC and ABC “drug” transporters, as well as drug metabolizing enzymes.

By understanding the mechanisms of these transporters, it may be possible to predict certain drug–drug interactions [88] and drug–metabolite interactions [88]. Regulation of OATs is a complicated process influenced by multiple intracellular signaling pathways and by various PTMs. Most studies have examined these regulatory factors in isolation. How they work in concert to modulate OAT function, to improve OAT‐related medical treatment, and to keep body homeostasis are important questions that will also provide insights into the workings of the remote sensing and signaling system.