SLC18A2 encodes vesicular monoamine transporter 2 (VMAT2), an electrogenic antiporter that packages monoamine neurotransmitters into synaptic vesicles for storage and exocytotic release 1. VMAT2 exchanges one cationic monoamine with two intravesicular protons, utilizing the proton gradient established by V-ATPase to accumulate high concentrations of dopamine, serotonin, noradrenaline, and histamine 2. This process is essential for proper monoaminergic neurotransmission, regulating both quantal size and synaptic transmission efficacy 1. Dysfunction of SLC18A2 is implicated in multiple neurological disorders. Reduced SLC18A2 expression correlates with Parkinson's disease pathology, appearing depleted in dopaminergic neurons and supporting glia in affected substantia nigra 3. Loss-of-function variants cause infantile-onset parkinsonism-dystonia 4. Additionally, SLC18A2 variants associate with tardive dyskinesia risk in antipsychotic-treated patients 5, and polymorphisms influence methamphetamine use disorder susceptibility and severity 6. Clinically, VMAT2 inhibitors (tetrabenazine, deutetrabenazine, valbenazine) represent FDA-approved therapeutics for hyperkinetic movement disorders including Huntington's disease and tardive syndromes, reducing excessive dopamine and serotonin release 78. Recent structural studies elucidate distinct drug inhibition mechanisms, enabling rational design of improved therapeutics 2.