MANF in cardiomyocytes interacts with BAX to impede BAX mitochondrial translocation and cytochrome c release, further stabilizing mitochondrial structure and energy supply to relieve myocardial apoptosis and hypertrophy, which indicates MANF as a novel cardioprotective factor to have a promising clinical application for myocardial hypertrophy. Here, CYCS is linked to cardiac hypertrophy.