We previously proposed that, in the setting of metabolic syndrome/diabetes, elevated tissue Ang-II induces NOX-mediated oxidative stress and loss of nephrin and podocin, leading to podocyte effacement and loss of slit pores diaphragms, and that these protein deficiencies and accompanying ultrastructural abnormalities are prerequisite to proteinuria/albuminuria [26]. The gene discussed is NPHS2; the disease is metabolic syndrome.