While patient hearts expressing the mutant FBXO32 protein unexpectedly showed either an absence or reduced activation of the three UPR branches, they show a strong upregulation of CHOP-mediated apoptosis and abnormally high levels of the ATF2 transcription factor, which binds FBXO32 and whose expression is abnormally high in mutant FBXO32 hearts and in cells expressing mutant FBXO32. These findings provide a new mechanism by which the FBXO32 mutation causes early-onset cardiomyopathy in human. Here, FBXO32 is linked to cardiomyopathy.