Our previous studies confirmed that the ALDH2*2 mutant allele is an independent risk factor for the severity of cardiac damage in myocardial infarction patients.[51, 52, 53] It has been reported that ALDH2 overexpression rescues cardiac contractile dysfunction in Alzheimer's disease via inhibiting ferroptosis.[54] In the present study, we found that ALDH2 cKO significantly exacerbated myocyte ferroptosis after MI/R by increasing GPX4 and OTUD5 carbonylation, which may be a new molecular mechanism underlying MI/R injury in patients with ALDH2 mutations. This evidence concerns the gene GPX4 and early-onset autosomal dominant Alzheimer disease.