By effectively reducing the expression of RBM20 either through genetic editing or antisense oligonucleotide (ASO)-mediated RNA degradation, researchers have demonstrated compelling evidence that upregulating larger TTN isoforms can significantly improve diastolic function in rodent models of heart failure with preserved ejection fraction (HFpEF) (Radke et al., 2021). Here, RBM20 is linked to heart failure.