NINJ2 (ninjurin 2) is a transmembrane adhesion molecule whose precise biological function remains unclear 1. Unlike its paralog NINJ1, NINJ2 cannot mediate plasma membrane rupture during programmed cell death due to structural differences in its filament assembly 1. Cryo-EM studies reveal that NINJ2 forms curved filaments that bend toward the intracellular space, preventing membrane circularization and cytolysis, in contrast to NINJ1's straight filaments 1. This curvature results from strong association with membrane lipids, particularly cholesterol at the cytoplasmic leaflet 1. NINJ2 appears to function as a homophilic adhesion molecule in nerve regeneration and axonal growth, though these roles require further validation. In disease contexts, NINJ2 shows significant clinical relevance: hepatocyte NINJ2 promotes liver fibrosis through IGF1R/EGR1/PDGF-BB signaling 2, and it contributes to neuroinflammation in Alzheimer's disease via the TLR4/NF-κB pathway 3. Genetic polymorphisms in NINJ2, particularly rs12425791, are associated with ischemic stroke susceptibility 4 and interferon-β treatment response in multiple sclerosis patients 5. The rs7298096 polymorphism affects NINJ2 expression levels and treatment outcomes, suggesting potential pharmacogenetic applications 6.