Mutations in the myocilin gene are responsible for autosomal-dominant inherited juvenile open-angle glaucoma as well as for some forms of primary open-angle glaucoma (POAG) in adults. Myocilin is a secreted glycoprotein with a molecular weight of 55-57 kDa that can form dimers and multimers. Structural components are a myosin-like domain, an olfactomedin domain and a leucine zipper. In patients with POAG, most mutations are situated in the olfactomedin domain, a region that is highly conserved in various species. In the eye, myocilin is produced in substantial amounts in the trabecular meshwork, sclera, ciliary body and iris, and at smaller levels in retina and optic nerve head. Secreted myocilin is also found in the aqueous humor. In the chamber angle, myocilin is closely associated with fibrillar components of the extracellular matrix that are found in the cribriform region of the trabecular meshwork. Myocilin binds specifically to the HepII domain of the matrix protein fibronectin. Recombinant myocilin increases outflow resistance of the trabecular meshwork in perfused organ cultures of anterior eye segments. In cultured trabecular meshwork cells, dexamethasone can induce the expression of myocilin in the same time course as observed in patients developing ocular hypertension after steroid treatment. Furthermore, myocilin can be induced by transforming growth factor-b1 and mechanical stress. Myocilin knockout mice feature no noticeable phenotype. This suggests that glaucoma with a mutation in the myocilin gene is not caused by a loss of function of myocilin. Experimental data indicate that mutated myocilin is not secreted, but accumulates within trabecular meshwork cells. The accumulation of myocilin might impair the function of the trabecular meshwork. Impairment of trabecular meshwork function might increase outflow resistance and might finally cause glaucoma.