SLC32A1 encodes the vesicular inhibitory amino acid transporter (VGAT), a proton-antiporter that loads gamma-aminobutyric acid (GABA) and glycine into synaptic vesicles for neurotransmitter release 1. The transporter exchanges vesicular protons for cytosolic GABA, enabling GABAergic neurotransmission at inhibitory synapses 2. SLC32A1 is the sole protein identified to date responsible for packaging GABA and glycine into synaptic vesicles 1. De novo missense variants in SLC32A1 cause developmental and epileptic encephalopathy (DEE114) characterized by moderate-to-severe intellectual disability, infantile-onset seizures, and movement disorders 1. Pathogenic variants impair GABAergic neurotransmission through two mechanisms: reduced synaptic vesicle GABA filling and altered presynaptic release probability 1. Inherited missense variants also cause genetic epilepsy with febrile seizures plus (GEFS+12) by altering GABA transport 2. Beyond epilepsy, SLC32A1 dysregulation associates with psychiatric and neurodegenerative conditions. In post-traumatic stress disorder, SLC32A1 is downregulated through hsa-mir-589-mediated mechanisms, contributing to GABAergic dysfunction 3. SLC32A1 expression marks early Alzheimer's disease pathology, particularly in dysfunctional synaptic signaling 4. The gene also influences metabolic homeostasis, with variants associated with circulating leptin levels independent of adiposity 5. SLC32A1 represents a critical node in GABAergic neurotransmission with broad relevance to neurological, psychiatric, and metabolic diseases.