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The serotonin transporter (SERT) is the target site for serotonin reuptake inhibitors, which are the most widely used agents for treating various psychiatric diseases including depression. The SERT is a member of a large family of homologous integral membrane proteins. This transporter takes up 5-HT in a process that is coupled to the transmembrane movement of Na+ , Cl- , and K+ . The SERT may operate in at least two modes, an alternating access carrier or a channel. The function of SERT is acutely regulated by various protein kinases and phosphatases. The SERT gene is located on chromosome 17 and has several polymorphisms including 5-HTTLPR and intron 2 VNTR. Most studies involving the association between 5-HTTLPR and the response to SSRI in depression reported that 1/1 genotype showed better response and fewer side effects. But, it is too early to draw definite conclusion of the effects of 5-HTTLPR on anti-depressant treatment. Therefore, it is necessary to perform further studies reflecting various ethnicities and genetics of subjects as well as the environmental interactions. This review discusses recent advances in defining the structure, the action mechanism, the location, and the regulation of SERT. Furthermore, it discusses the function of SERT polymorphisms and its implications on the anti-depressant therapies.
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