{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leucine‐rich, glioma‐inactivated 1 (LGI1) is a secreted neuronal protein that plays a central role in the organization and stabilization of synaptic circuits, particularly within the temporal lobe. Clinical and genetic studies have demonstrated that LGI1 is critical for normal synaptic function by binding to its neuronal receptors ADAM22 and ADAM23, thereby regulating the clustering of synaptic proteins such as AMPA receptors and voltage‐gated potassium channels that modulate presynaptic neurotransmitter release and control dendritic pruning. This interaction is essential for the appropriate maturation of glutamatergic synapses and the maintenance of circuit excitability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Dysregulation of LGI1 function occurs via distinct mechanisms. Autoantibodies targeting LGI1 are now recognized as the pathogenic mediators in limbic encephalitis, an autoimmune synaptic encephalopathy characterized by seizures and memory impairment; the pathogenic relevance of these autoantibodies underscores the importance of intact LGI1–receptor interactions in maintaining normal neuronal signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, loss‐of‐function mutations in the LGI1 gene have been causally linked to autosomal dominant partial (lateral temporal) epilepsy with auditory features. Reduced secretion or impaired binding of mutant LGI1 disrupts its regulatory control over excitatory synaptic transmission, leading to enhanced glutamate release and network hyperexcitability that culminates in seizure generation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings indicate that LGI1 functions as an essential synaptic organizer that fine‐tunes neuronal excitability and proper circuit formation. Disruption of LGI1—whether via autoimmune mechanisms or genetic mutations—leads to impairments in synaptic receptor composition and ion channel regulation, ultimately predisposing affected individuals to epileptic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Meizan Lai, Maartje G M Huijbers, Eric Lancaster, et al. 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