Numerous transport proteins have been identified and cloned from different tissues during the past years. In the process of their functional characterization it became clear that various drugs are substrates or inhibitors of the so-called drug transporters that include the P-glycoproteins, the multidrug related proteins (Mrps/MRPs) and the organic anion transporting polypeptides (rodents: Oatps; human: OATPs).

Oatps/OATPs form a growing gene superfamily of currently 28 members in man, rat and mouse and mediate Na⁺-independent transport of a wide spectrum of mainly amphipathic organic solutes. Based on their amino acid homology they can be grouped into five different families. The proteins with the broadest spectrum of amphipathic transport substrates are clustered in family 1. These OATP1-family members are thought to be part of the overall body detoxification system and help to remove potentially toxic endo- and xenobiotics from the systemic circulation. In the liver, an important organ for the elimination of a wide variety of mainly amphipathic endo- and xenobiotics, several of these family members are expressed at the sinusoidal membrane (rat Oatp1, Oatp2 and Oatp4, human OATP-C and OATP8) and mediate uptake into hepatocytes. Functional characterization revealed that these Oatps/OATPs transport in a sodium-independent way a wide variety of mainly bulky organic anions, neutral compounds, organic cations and several drugs like e.g. statins, cardiac glycosides, ACE-inhibitors, endothelin-antagonists and antihistamines. Besides liver-specific Oatps/OATPs (Oatp4, OATP-C and OATP8) there are others that are expressed in various tissues including intestine (Oatp3), kidney (Oatp1, OAT-K1, OATP-A), brain (Oatp2, Oatp3, OATP-A, and OATP-F) and testis (OATP-F). Their expression in these multiple tissues puts them into a strategic position for absorption, distribution and excretion of drugs and toxins.

Although the exact physiological functions of most Oatps/OATPs remain to be elucidated, nearly all Oatps/OATPs of families 2-4 have narrower substrate specificities (e.g. OATP-B, OATP-E) and may serve more specific functions in selected organs such as for example thyroid hormone transport in various peripheral organs, or steroid and steroid metabolite transport in adrenal gland and placenta. Thus, the functional diversity of the OATP superfamily could be very similar to the CYP450 superfamily where only families 1-4 are involved in metabolism and detoxification of drugs and environmental chemicals, whereas the members of the other families catalyse specific pathways in the cholesterol, prostacyclin and/or steroid metabolism.

Based on their selective tissue distribution and substrate specificities, Oatps/OATPs could eventually be used to target drugs to certain organs. However, an accurate determination of their expression as well as an exact delineation of their substrate specificities is a prerequisite to use them for a more rational drug design.