SLC6A2 encodes the norepinephrine transporter (NET), a plasma membrane protein that mediates sodium- and chloride-dependent reuptake of norepinephrine from the synaptic cleft, terminating noradrenergic neurotransmission 1. NET plays a critical role in norepinephrine homeostasis and inactivation in the autonomic sympathetic nervous system 234. The transporter can also transport dopamine via similar sodium- and chloride-dependent mechanisms 5367. Structurally, NET utilizes a central substrate binding site and an extracellular allosteric site for substrate recognition, with coordinated Na+ and Cl- binding undergoing conformational changes during transport 17. NET is post-translationally modified by palmitoylation, affecting membrane localization and function 8. Clinically, SLC6A2 polymorphisms associate with psychiatric disease susceptibility, including major depressive disorder with suicide attempts 9 and PTSD-related neuroimaging abnormalities 10. SLC6A2 genetic variants influence atomoxetine treatment response in ADHD 11. NET is a major pharmacological target for antidepressants (bupropion, desipramine, atomoxetine, escitalopram, paroxetine) and analgesic drugs 712, and mutations cause orthostatic intolerance.