Fibronectin (Fn) is a glycoprotein whose size ranges from 230 to 270 kDa and usually exists as a dimer, covalently linked by a pair of disulfide bonds at the C-termini. Each monomer consists of three repeating units: 12 Type I, 2 Type II, and 15–17 Type III domains which combined account for 90% of the FN sequence. The extracellular matrix (ECM) plays a key role as both structural scaffold and regulator of cell signal transduction in tissues. Fibronectin is one of the major ECM proteins in the trabecular meshwork (TM). It is found in the sheath material surrounding the elastin tendons that enter the TM from the ciliary muscle within the ciliary body. In times of ECM assembly and turnover, cells upregulate assembly of the ECM protein, FN. FN is assembled by cells into viscoelastic fibrils that can bind upward of 40 distinct growth factors and cytokines. These fibrils play a key role in assembling a provisional ECM during embryonic development and wound healing. Fibril assembly is also often upregulated during disease states, including cancer and fibrotic diseases.