Many physiological, endocrine and behavioral functions are determined and regulated by monoamine signaling^1,2. Many brain disorders such as depression, drug abuse, schizophrenia, attention deficit hyperactivity disorder (ADHD) are caused by the malfunction of monoaminergic transmission^1-3.  The intensity of monoaminergic signaling is determined by the availability of the monoamine, which is in turn determined in part by its uptake from the extracellular milieu via monoamine transporters. These transporters include DAT, SERT, and NET, responsible for uptaking dopamine, serotonin (5-HT) and noradrenaline respectively, and recycling them back for release^3-5.

DAT, SERT and NET are members of the Na⁺/Cl^- dependent membrane transporter family which also includes other members. These transporters consist of 12 transmembrane domains and intracellular N- and C-termini. Like its counterparts, SERT’s intracellular N- and C-terminal domains are also subject to phosphorylation and protein-protein interactions important for modulating its activity and localization⁶.

SERTs are evidently expressed in serotonergic neurons, and are also expressed in various peripheral tissues including specialized cells of the gut, placenta, lung, blood lymphocytes and platelets⁶.

SERT knockout mice are viable and as a consequence exhibit increased extracellular levels of 5-HT and significantly decreased levels of brain tissue 5-HT due to deficient recycling and re-accumulation of serotonin by SERT⁷. Phenotypes displayed by SERT knockout mice include stress sensitivity, obesity and various behavioral changes. ⁸