The structural insights gained from the cryo-EM analysis of the human noradrenaline transporter (NET) provide crucial information for the development of targeted and effective treatments for disorders associated with noradrenaline dysregulation. By understanding the binding modes of substrates like noradrenaline and dopamine within the central substrate binding site (S1) and the extracellular allosteric site (S2), researchers can design molecules that specifically target these sites to modulate NET function. Additionally, the identification of distinct conformations in which antidepressants like atomoxetine, desipramine, bupropion, and escitalopram obstruct substrate transport sheds light on potential drug design strategies. This knowledge allows for the development of more precise medications that can selectively modulate NET activity, leading to improved therapeutic outcomes with reduced side effects.