Deletion of the arginine 14 codon (R14del) in the phospholamban gene (PLN), which encodes a protein that inhibits Ca2+ uptake by SERCA2a, is associated with inherited dilated cardiomyopathy. Heterozygous patients have ventricular dilatation, contractile dysfunction, ventricular arrhythmias, and heart failure. Stillitano et al. obtained induced pluripotent stem cells (iPSCs) from a patient with a PLN R14del mutation and differentiated them into cardiomyocytes. Gene editing to correct the PLN mutation was performed with transcriptor activator-like effector nucleases (TALENs). Using 3D human engineered cardiac tissue (hECT) technology, the researchers found that the mutant hECTs had a lower excitation threshold potential (suggesting susceptibility to arrhythmogenesis), a lower developed twitch force amplitude, and slower maximum rates of contraction and relaxation, compared with corrected hECTs. “This study,” conclude the investigators, “lays the groundwork for targeted gene therapy for treating patients with hereditary forms of cardiomyopathy.”