Emerging Roles of the Human Solute Carrier 22 Family

Abstract

The human solute carrier 22 family (SLC22), also termed the organic ion transporter family, consists of 28 distinct multi-membrane spanning proteins, which phylogenetically cluster together according to their charge specificity for organic cations (OCTs), organic anions (OATs), and organic zwitterion/cations (OCTNs). Some SLC22 family members are well characterized in terms of their substrates, transport mechanisms, and expression patterns, as well as their roles in human physiology and pharmacology, whereas others remain orphans with no known ligands. Pharmacologically, SLC22 family members play major roles as determinants of the absorption and disposition of many prescription drugs, and several, including the renal transporters, OCT2, OAT1 and OAT3, are targets for many clinically important drug-drug interactions. In addition, mutations in some of these transporters [SLC22A5 (OCTN2) and SLC22A12 (URAT1)] lead to rare monogenic disorders. Genetic polymorphisms in SLC22 transporters have been associated with common human disease, drug response, and various phenotypic traits. Three members in this family were deorphaned very recently: SLC22A14, SLC22A15, and SLC22A24, and found to transport specific compounds, such as riboflavin (SLC22A14), anti-oxidant zwitterions (SLC22A15) and steroid conjugates (SLC22A24). Their physiologic and pharmacological roles need further investigation. This review aims to summarize the substrates, expression patterns and transporter mechanisms of individual SLC22 family members and their roles in human disease and drug disposition and response. Gaps in our understanding of SLC22 family members are described.