SLC6A1 encodes GAT1 (GABA transporter 1), which mediates the sodium- and chloride-dependent reuptake of gamma-aminobutyric acid (GABA) from synapses into neurons and astrocytes 1. This transporter plays a pivotal role in GABAergic neurotransmission by clearing GABA from the synaptic cleft and facilitating its storage in presynaptic vesicles 2. The protein functions through a complex intracellular trafficking process involving molecular chaperones, quality control mechanisms, and delivery to the cell surface 2. Pathogenic variants in SLC6A1 cause a broad spectrum of neurological disorders, including myoclonic-atonic epilepsy and developmental epileptic encephalopathies 3. Many disease-causing mutations impair protein folding and membrane targeting, leading to loss of transporter function and disrupted GABAergic signaling 23. Complete loss of GABA uptake function is associated with more severe clinical phenotypes 3. Haploinsufficient deletions of SLC6A1, as seen in 3p- syndrome, also significantly reduce GABA uptake capacity 4. Gene therapy approaches using AAV9 vectors have shown promise in preclinical models, normalizing EEG patterns and improving behavioral deficits 1. Additionally, pharmacological chaperones like 4-phenylbutyrate can rescue some misfolded variants and provide therapeutic benefits 24.