The review integrates current knowledge in POAG from human and experimental data and dissects the contribution of the newly discovered genetic loci with the known molecular and biological processes, including extracellular matrix remodeling; TGF-β and tumor necrosis factor α (TNF-α) signaling; and the vascular tone pathway, that have been implicated in the pathogenesis of POAG. The gene discussed is TGFB1; the disease is open-angle glaucoma.