MMRN2 is an extracellular matrix glycoprotein that plays dual regulatory roles in vascular biology. As a primary function, MMRN2 maintains vascular stability and integrity by promoting cell-cell junctional stability in endothelial cells 1. It acts as a ligand for the CD93 receptor, positively regulating angiogenesis through this interaction 2. However, MMRN2 also exerts angiostatic properties by directly binding VEGF-A with high affinity (~50 nM), thereby sequestering this pro-angiogenic cytokine and reducing VEGFR2 activation 3. During angiogenic stimulation, MMRN2 expression decreases via MMP-9-mediated proteolytic cleavage, allowing sprouting angiogenesis to proceed 4. MMRN2 also binds CLEC14A to regulate sprout initiation 5. Clinically, MMRN2 dysfunction has significant implications: mutations in MMRN2 are associated with poor survival outcomes in lung adenocarcinoma patients 6, while elevated expression in tumor-associated vessels impairs chemotherapy efficacy through defective vascular perfusion 1. In corneal neovascularization, miR-1910-5p-mediated suppression of MMRN2 promotes pathological angiogenesis 7. MMRN2 expression levels may serve as a biomarker for predicting therapeutic response and vascular phenotype.