Fibronectin (FN) is a large, modular glycoprotein that generates a polymeric fibrillar network in the extracellular matrix (ECM), and forms soluble, disulfide-linked dimeric protomers in plasma and other body fluids (1, 2). Fibronectin is a ligand for many molecules, including fibrin, heparin, chondroitin sulfate, collagen/gelatin, and integrins. It is involved in multiple cellular processes such as cell adhesion/migration, blood clotting, morphogenesis, tissue repair, and cell signaling. Fibronectin functions are mediated by the insoluble polymeric fibrillar network. Conversion of soluble Fibronectin to Fibronectin fibrils in the ECM is initiated by binding to cell surface integrins, resulting in exposure of cryptic epitopes necessary for polymerization (1). Fibronectin is made up of three types of homologous structural motifs termed FN type I, type II, and type III repeats (3-5). Alternative splicing generates multiple isoforms of Fibronectin which may have insertions of extra type III domains (EDA and EDB) or alteration of the type III connecting segment (IIICS) (5). Differential splicing within the IIICS domain determines the presence of CS1 and CS2 sequences, and its sensitivity to proteases (6, 7). The tilt angle between type III domains #9 and #10 (which contains an RGD motif) determines integrin binding affinity, suggesting how structural differences between fibrillar and soluble Fibronectin may influence their function (8). From the N-terminus to the furin cleavage site at amino acid 1908, human Fibronectin shares 92% amino acid sequence identity with mouse and rat Fibronectin.