We confirmed that TBX20 and CASZ1 interact biochemically and genetically, and we go on to show that while mice singularly haploinsufficient for Tbx20 or Casz1 are asymptomatic, mice heterozygous for both Tbx20 and Casz1 die, beginning at 4 to 8 weeks post birth, and exhibit cardiomyocyte hypertrophy, interstitial fibrosis, and severe DCM. This evidence concerns the gene CASZ1 and familial dilated cardiomyopathy.