NID2 (nidogen-2) is a basement membrane glycoprotein that functions as a critical extracellular matrix (ECM) component mediating cell-matrix interactions through binding to collagens I and IV, perlecan, and laminin 1 1. In vascular biology, NID2 maintains vascular smooth muscle cell contractile phenotype by bridging Jagged1-Notch3 signaling, with NID2 deficiency leading to aggravated neointima formation following vascular injury 1. NID2 plays dual disease-relevant roles: as a metastasis suppressor in nasopharyngeal and esophageal cancers through inhibition of EGFR/Akt and integrin/FAK signaling 2, yet as a cancer promoter in glioma via Akt pathway activation and in pancreatic cancer where cancer-associated fibroblast-derived NID2 enhances fibrosis and therapy resistance 34. NID2 overexpression promotes hepatosteatosis and atherosclerosis through reduced AMPK activation 5. Clinically, NID2 expression serves as a prognostic biomarker: high expression predicts worse outcomes in glioma and correlates with glioma grade 3, while NID2 promoter methylation is significantly elevated in multiple cancers and represents a target for blood-based multi-cancer early detection 6. Genetic variants in NID2 (rs11846847, rs1874569) associate with increased glioma risk and poor prognosis in Asian populations 7.