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). Here, TNFRSF12A is linked to cardiac hypertrophy.