With the cardiac-specific MG53 transgenic mice, Liu et al. showed that, in addition to IRS-1 downregulation, MG53 can be found in the nucleus of cardiomyocytes to modulate transcriptional activation of PPARα signaling30, and the elevated PPARα activity could contribute to the hypertrophy and cardiomyopathy observed in their mouse cohort. The gene discussed is IRS1; the disease is cardiomyopathy.