LINGO2 is a transmembrane signaling receptor containing leucine-rich repeats and immunoglobulin domains, located on chromosome 9. As a synaptic organizer, LINGO2's soluble extracellular domain (sLingo2), generated by ADAM10-mediated proteolysis, promotes excitatory synapse formation and increases miniature excitatory postsynaptic current frequency in neurons 1. LINGO2 dysfunction is implicated in multiple neurodegenerative and metabolic disorders. In Alzheimer's disease pathogenesis, LINGO2 is upregulated in APPV717I neurons and postmortem AD tissue; downregulation of LINGO2 rescues neurite outgrowth deficits and reverses AD-associated transcriptional changes in synaptic function and cellular stress 2. Mechanistically, m6A methylation of LINGO2 mRNA by Mettl3 promotes its degradation via Ythdf2, reducing LINGO2 levels and enhancing APP-BACE1 interaction, thereby increasing amyloid-β production 3. Genetic variants in LINGO2 (rs10968576, rs1412239) significantly increase gestational diabetes mellitus risk, particularly through gene-environment interactions with air pollution and BMI 4. LINGO2 polymorphisms also associate with Parkinson's disease and essential tremor susceptibility, influencing disease onset age 56. These findings establish LINGO2 as a multifunctional synaptic organizer with therapeutic potential in neurodegeneration and metabolic disease.