RBM20 and cardiac hypertrophy: HMGCS2 is a critical mitochondrial enzyme that catalyses the rate-limiting step in ketogenesis and may affect the heart’s ability to efficiently manage metabolic stress.46,47 Additionally, cardiac proteomics of Rbm20 KO rats revealed the up-regulation of Ankrd1, which promotes hypertrophic gene expression,48,49 and the down-regulation of FHL2, a negative regulator of cardiac hypertrophy.46,50 The combined effect of increased Ankrd1 and decreased FHL2 expression could contribute to the development of hypertrophic remodelling.