Taken together, our findings suggest that the genetically engineered SPEG E1680K human iPSC-CMs recapitulated the hallmark phenotypes associated with DCM, including sarcomeric disorganization, aberrant Ca2+ homeostasis and contractile defects, suggesting that SPEG E1680K is a pathogenic variant. The gene discussed is SPEG; the disease is familial dilated cardiomyopathy.