ASMase increases ROS production by stimulating NOX4 expression, thereby triggering cell apoptosis. This effect is completely blocked by an ASMase inhibitor or ASMase knockout. In vivo experiments further demonstrate that ASMase deficiency can reverse heart disease induced by a high-fat diet (HFD) in mice, resulting in improved cardiac function, reduced hypertrophy, fibrosis, and apoptosis. The gene discussed is NOX4; the disease is heart disorder.