The leucine-rich glioma inactivated (LGI) gene subfamily contains four highly conserved members (LGI1, 2, 3 and 4), which have been described in human, mouse and other mammalians. LGI1 is mainly expressed in the dentate gyrus and the CA3 field of the hippocampus¹.

The predicted structure of the LGI1 protein comprises, starting from the N-terminal, a signal peptide, four leucine-rich repeats (LRR) flanked on both sides by conserved cysteine clusters, and seven copies of a repeat of about 45 residues, named EPTP or EAR, probably forming a β-propeller structural domain. Both LRR and β-propeller domains mediate protein-protein interactions, each motif defining a distinct family of proteins.

LGI1 is associated with a post-synaptic complex containing PSD-95 and ADAM22, a receptor associated with the post-synaptic membrane. Through specific binding to ADAM22, LGI1 participates in the control of synaptic strength at excitatory synapses, whose malfunction may result in epilepsy.

LGI1 has been linked to several different clinical phenotypes including: malignant progression of glioma and autosomal dominant lateral temporal epilepsy, a rare familial partial epilepsy syndrome. The LGI1 gene has been shown to be frequently downregulated in malignant gliomas and to regulate invasiveness of some glioma cell lines by driving the expression of matrix metalloproteinases through the ERK 1/2 pathway. These findings suggest that LGI1 may serve as a tumor metastasis suppressor gene². In addition, antibodies to LGI1 complexed with the K_V1.1 potassium channel have been found in brain extracts from patients with limbic encephalitis³.