SLC6A2 encodes the norepinephrine transporter (NET), a sodium- and chloride-dependent symporter that mediates reuptake of norepinephrine from the synaptic cleft into presynaptic neurons, thereby terminating noradrenergic signaling and maintaining neurotransmitter homeostasis 1. The transporter also transports dopamine via the same mechanism 2. Recent cryo-electron microscopy structures reveal that norepinephrine binds in a central substrate-binding pocket and that NET exists as a dimer stabilized by cholesterol and lipid interactions 3. The transporter undergoes conformational changes between inward- and outward-facing states to couple ion gradients with substrate translocation 4. SLC6A2 dysfunction is implicated in multiple neuropsychiatric and pain conditions, including depression, anxiety disorder, attention deficit hyperactivity disorder, and chr16 pain. SLC6A2 polymorphisms associate with suicide risk in major depressive disorder 5 and with hypertension in Japanese populations 6. Structurally characterized antidepressants including atomoxetine, desipramine, bupropion, amitriptyline, and escitalopram inhibit NET by occupying the substrate-binding site or stabilizing conformations that prevent transport 2. These drugs are widely used to treat depression, anxiety, and attention deficit hyperactivity disorder.