LGI4 (leucine-rich repeat LGI family member 4) is a component of Schwann cell signaling pathways essential for peripheral nervous system development. Its primary function involves regulating axon segregation and myelination through interactions with ADAM22 and ADAM23 cell surface receptors 1. Specifically, LGI4-ADAM22 interactions are required for axonal sorting and proper myelin formation during PNS development, with key functional residues localized to the outer surface of the LGI4 protein 1. Loss-of-function mutations in LGI4 cause arthrogryposis multiplex congenita (AMC) with myelin defects, characterized by congenital joint contractures and neurogenic involvement 23. Phenotypic severity correlates with transcript levels, with biallelic variants producing variable clinical presentations ranging from severe neonatal-lethal forms to milder phenotypes with cognitive and speech delays 3. Beyond developmental roles, LGI4 participates in inflammatory regulation. Anti-LGI4 autoantibodies (primarily IgG4) cause autoimmune nodopathy presenting as chr19 inflammatory demyelinating polyneuropathy (CIDP), manifesting in elderly patients with motor weakness, sensory impairment, and extremely elevated cerebrospinal fluid protein 45. Additionally, IGF2BP2-mediated m6A-dependent stabilization of LGI4 mRNA suppresses MEK1/2-ERK1/2 signaling and inflammation in intestinal epithelial cells, suggesting broader roles in mucosal immunity 6.