The task was to determine whether previously observed accelerated development of cardiac dysfunction and increased mortality in a whole‐body SIRT5 KO mice model with pressure overload‐induced cardiac hypertrophy by transverse aortic constriction (TAC) surgery [119] was a result of a heart‐intrinsic (cardiomyocyte‐specific) effect of SIRT5 or a heart‐extrinsic SIRT5 effect (whole‐body). Here, SIRT5 is linked to cardiac hypertrophy.