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Target intelligence / Profile preview
Leucine-rich repeat LGI family member 2 (LGI2)
- Target
- LGI2
- Molecular classification
- Secreted protein, Extracellular modulator, Leucine-rich repeat (LRR) family protein
01
Overview
Leucine-rich repeat LGI family member 2 (LGI2) is a secreted protein belonging to the LGI family, characterized by leucine-rich repeat and beta-propeller (EPTP/EAR) domains. LGI2 is predominantly expressed in neuronal tissues, particularly in regions involved in hippocampal rhythm generation and synaptic synchronization. It modulates synaptic transmission by acting as an extracellular organizer, and its proper secretion and folding are critical for maintaining inhibitory synapse function and balanced neuronal excitability. Disease-associated LGI2 mutations result in secretion deficits and abnormal retention in the endoplasmic reticulum, leading to epilepsy syndromes (notably familial partial epilepsy with pericentral spikes in humans and juvenile remitting epilepsy in dogs). LGI2 interacts with ADAM family proteins (ADAM11, and potentially ADAM22/ADAM23), contributing to synaptic maturation at specific developmental windows. While LGI2 itself is not directly targeted by approved drugs, its genetic variants serve as biomarkers for diagnosis and disease risk stratification.
- Other names
- KIAA1916LGIL2FLJ10675LGI1-like protein 2Leucine-rich glioma-inactivated protein 2leucine-rich repeat LGI family member 2leucine-rich, glioma inactivated 2
02
Biological functions
Inhibitory synapse assemblyModulation of neuronal excitabilitySynaptic maturationRegulation of extracellular matrix interactionsNeuronal network constructionRequired for development of soma-targeting inhibitory GABAergic synapses made by parvalbumin-positive basket cells
03
Disease associations
Epilepsy (familial partial epilepsy with pericentral spikes; juvenile remitting epilepsy in dogs)Congenital contracture syndromes (Arthrogryposis multiplex congenita-1)
04
Safety considerations
Mutations lead to secretion deficiency and intracellular retention, causing epilepsyTherapeutic challenges include precisely targeting synaptic mechanisms and avoiding disruption of normal network development
05
Biomarkers
Disease-causing mutation for canine juvenile epilepsyCandidate gene for familial partial epilepsy in humansMutational analysis for disease diagnosis
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