IGFBP2 is a multifunctional extracellular protein that regulates insulin-like growth factor (IGF) signaling and cellular processes including proliferation, differentiation, and apoptosis 12. The protein functions coordinately with receptor protein tyrosine phosphatase beta and IGF1 receptor to stimulate PTEN phosphorylation and AKT1 activation 3. IGFBP2 promotes cell migration via RGD motif interaction with integrin α5β1 4 and enhances endothelial progenitor cell adhesion 5. Upon mitochondrial damage, IGFBP2 facilitates podocyte apoptosis through focal adhesion kinase-mediated pathways 2. Clinically, IGFBP2 dysregulation associates with multiple disease pathologies. In hepatocellular carcinoma, matrix stiffness upregulates IGFBP2 expression via the integrin β1/Piezo1/HIF-1α pathway to promote angiogenesis 6. Conversely, IGFBP2 loss in alveolar type 2 cells promotes senescence and lung fibrosis, while restoring IGFBP2 levels ameliorates bleomycin-induced fibrosis and pulmonary hypertension 7. In pulmonary hypertension, endothelial FUNDC1 deficiency increases IGFBP2 secretion, driving pulmonary arterial remodeling 8. In glioma, cancer-associated fibroblast-derived IGFBP2 promotes M2 macrophage polarization and tumor progression 9. Notably, IGFBP2 administration significantly reduces neuronal loss and improves functional recovery following spinal cord injury 10, highlighting its therapeutic potential.