Altogether, our data reveal a new therapeutic avenue for DCM patients with disease-causing variants in the RS-rich region of RBM20. Since the majority of TNPO3 targets52 were detectably expressed in iPSC-CMs (Supplementary Data 13), direct overexpression of TNPO3 may affect their nuclear import resulting in potential side-effects of therapeutic TNPO3 overexpression. Here, RBM20 is linked to familial dilated cardiomyopathy.