EMILIN2 (elastin microfibril interfacer 2) is an extracellular matrix glycoprotein with multifaceted roles in vascular biology and cancer regulation. Structurally, EMILIN2 contains an N-terminal EMI domain and C-terminal gC1q domain that enable homo- and hetero-multimerization with EMILIN1 1, facilitating its assembly within the extracellular matrix. Primary functions include promoting vascular stability through pericyte recruitment—EMILIN2 stimulates endothelial cells to release PDGF-BB and HB-EGF, serves as an adhesion substrate via α5β1 and α6β1 integrin engagement, and enhances N-cadherin-mediated endothelial-pericyte interconnection 2. EMILIN2 also regulates hemostasis by promoting platelet aggregation and clot retraction through outside-in signaling 3. In cancer, EMILIN2 exhibits tumor-suppressive effects by directly binding WNT1 ligand, inhibiting canonical WNT signaling and reducing breast cancer cell viability and migration 4. However, HPV-18 E6 oncoprotein disrupts this mechanism by enhancing EMILIN2-SNX27 interaction, thereby blocking EMILIN2-mediated WNT inhibition and promoting proliferation 5. Low EMILIN2 expression correlates with poor prognosis in low-grade gliomas and ovarian cancer, where p53 transcriptionally regulates EMILIN2 to suppress the Warburg effect [PMID:34280481; 68]. Clinically, EMILIN2 represents a promising prognostic biomarker and potential therapeutic target for multiple cancer types.