Leucine-rich repeat LGI family member 3 (LGI3)

Leucine-rich repeat LGI family member 3 (LGI3) is a secreted protein belonging to the LGI family, primarily expressed in the brain, but also found in the skin, adipose tissue, and various other organs[1]. LGI3 has structural domains characterized by tandem leucine-rich repeats and epitempin repeats, suggesting a role in protein-protein interactions and extracellular signaling[1][2]. In the nervous system, oligodendrocyte-derived LGI3 localizes at the juxtaparanodes of myelinated axons, where it recruits its receptor, ADAM23, and co-assembles with Kv1 potassium channels, thereby organizing specialized nanoclusters that are critical for proper synaptic transmission and plasticity[2]. LGI3 also acts as a multifunctional cytokine outside the nervous system, regulating adipogenesis, skin pigmentation, and inflammation through both direct effects and interaction with other cytokines such as TNF-α[1]. Clinically, LGI3 is implicated in several disorders: genetic variants are linked to intellectual disability, LGI3 expression is associated with prognosis in several cancers, and it plays a role in metabolic inflammation observed in obesity[1][2]. While there are no drugs currently reported to directly target LGI3, its signaling pathway, especially LGI3–ADAM23–Kv1 axis, is of significant interest for neurodevelopmental and oncological research[2].

Other names

LGI3LGIL4IDDMDSUNQ8190/PRO23199LGI1-like protein 4Leucine-rich glioma-inactivated protein 3leucine-rich repeat LGI family member 3