TNXB encodes tenascin-X (TN-X), an extracellular matrix glycoprotein that mediates cell-matrix interactions and regulates vascular homeostasis. TN-X inhibits cell migration and promotes collagen fibril organization 1, functioning as an anti-adhesive ECM protein 1. Mechanistically, TN-X binds directly to transforming growth factor-β (TGF-β) through its fibrinogen-like domain, blocking TGF-β receptor activation 2. In endothelial cells, laminar flow upregulates TN-X expression in a KLF4-dependent manner, suppressing endothelial-to-mesenchymal transition (EndMT) and atherosclerosis 2. Similarly, TN-X regulates vascular smooth muscle cell plasticity by inhibiting TGF-β signaling during vascular remodeling 3. TNXB mutations cause tenascin-X deficiency-associated Ehlers-Danlos syndrome, characterized by skin hyperelasticity and connective tissue fragility 14. TNXB variants are also associated with congenital anomalies of the kidney and urinary tracts (CAKUT) 5, and TNXB expression may serve as a prognostic biomarker in medullary thyroid carcinoma 6. Mutations in benign joint hypermobility syndrome involve tenascin-X 7, suggesting broader roles in connective tissue integrity.