Cell culture as well as in vivo experiments have indicated that TWEAK/Fn14 signaling is involved in cardiac hypertrophy, cardiac remodeling, and heart failure, identifying TWEAK and Fn14 as promising targets to treat CVDs (30, 45, 58, 59, 69, 70, 99, 137). The gene discussed is TNFRSF12A; the disease is heart failure.