SNED1 is an extracellular matrix (ECM) glycoprotein containing sushi, nidogen, and EGF-like domains that plays critical roles in developmental morphogenesis and cancer progression. 1 During development, SNED1 is essential for survival and craniofacial development; homozygous knockout results in early neonatal lethality with craniofacial malformations and nasal cavity occlusion, particularly affecting neural crest cells undergoing epithelial-to-mesenchymal transition. 1 SNED1 mediates cell adhesion through RGD and LDV motifs that bind integrin cell surface receptors, specifically α5β1 and αvβ3, facilitating both neural crest cell migration and cell-ECM interactions. 2 The protein forms microfibrils within the ECM and interacts with fibronectin and potentially 114 other proteins involved in integrin signaling and ECM organization. 3 In cancer, SNED1 promotes breast cancer metastasis, with elevated expression negatively correlating with patient survival in ER(-)/PR(-) tumors. 4 Additionally, SNED1 expression is dysregulated in disease states including diabetic nephropathy, glioblastoma, and childhood obesity-related metabolic changes, suggesting broader pathophysiological relevance. 5 6 7 These findings establish SNED1 as a multifunctional ECM protein bridging developmental biology and cancer biology through integrin-mediated signaling.