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 and noradrenaline respectively, and recycling them back for release^3-5.

While the activity of each transporter is faithful to its neurotransmitter, NET has been shown to clear dopamine in DAT deprived or low DAT regions such as the brain cortex^6-8.

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. NET also has a significant extracellular loop between transmembrane regions three and four, which contains various glycosylation sites⁹. Like its counterparts, NET’s intracellular N- and C-terminal domains are also subject to phosphorylation and protein-protein interactions important for modulating its activity and localization. In addition alternative splicing has also been shown to regulate NET’s expression and function¹⁰.

NET is specifically expressed on noradrenaline nerve terminals, and is also expressed in the periphery, such as adrenal glands and placenta. NET malfunction is largely associated with attention and mood, as well as various cardiovascular disorders. NET is also a target for psychostimulants such as cocaine and amphetamines which disrupt its function, thereby causing an increase of noradrenaline in synaptic clefts^3,9.