{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC6A11 encodes the γ‐aminobutyric acid (GABA) transporter subtype 3 (GAT‑3), a protein that is primarily expressed in astrocytes and plays a crucial role in clearing GABA from the synaptic cleft. This regulatory function is essential for maintaining inhibitory neurotransmission and overall synaptic homeostasis. In models of alcohol addiction, for example, reduced GAT‑3 expression in the amygdala appears to impair GABA clearance, which is associated with enhanced alcohol‐seeking behavior, while similar reductions have been observed in Alzheimer’s disease astrocytes, where altered uptake contributes to disrupted neurotransmitter metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic association studies have implicated SLC6A11 in several neuropsychiatric and neurological disorders. Polymorphisms in SLC6A11 have been linked with susceptibility to neuroleptic-induced tardive dyskinesia and with pharmacoresistance in epilepsy, suggesting that even subtle changes in GAT‑3 function or expression can influence drug response and disease risk. Furthermore, alterations in SLC6A11 expression due to small chromosomal deletions have been connected to a spectrum of developmental abnormalities—including intellectual disability, epilepsy, and ataxia—thereby reinforcing its broad role in modulating inhibitory signaling in the brain."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, SLC6A11 is involved in a finely tuned process that couples GABA transport with sodium (and chloride) ion gradients, a feature that has been explored by molecular dynamics and docking simulations. Structural investigations contribute to understanding the conformations that GABA and associated ions adopt during transport, while novel mass spectrometry‐based binding assays have been developed to characterize potent inhibitors of GAT‑3—an important step towards targeting this transporter for pharmacotherapy. Moreover, studies of microdeletions affecting the genomic region containing SLC6A11 underscore its potential contribution to complex phenotypes beyond synaptic signaling alone."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eric Augier, Estelle Barbier, Russell S Dulman, et al. 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