The leucine-rich glioma-inactivated 4 (LGI4) protein, a member of the LGI family (LGI1-4), is primarily expressed in the nervous system and plays critical roles in neural development and function. Unlike its well-studied paralog LGI1 (associated with autoimmune encephalitis), LGI4 is implicated in regulating peripheral nervous system myelination by interacting with ADAM22/23 receptors, influencing Schwann cell differentiation and axonal integrity.
Anti-LGI4 antibodies have recently emerged as potential biomarkers in neurological disorders. Studies link these antibodies to autoimmune neuropathies, such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP), where they may disrupt LGI4-ADAM22/23 signaling, impairing myelin maintenance. Notably, anti-LGI4 autoantibodies were identified in subsets of patients with paranodopathy, correlating with conduction block and treatment resistance.
Additionally, LGI4 dysregulation is observed in cancers (e.g., glioblastoma, breast cancer), though its pathogenic role and therapeutic targeting remain under investigation. Research on anti-LGI4 antibodies is still evolving, with most data derived from animal models or small patient cohorts. Further validation is needed to clarify their diagnostic utility, pathophysiological mechanisms, and therapeutic implications in autoimmune and neoplastic contexts. (Word count: 199)