TOMM40/APOE locus was associated with the main risk factors for cardiovascular disease; Homozygous deletion of TOMM40 in mammals was lethal; Heterozygous TOMM40 knockdown mice with ECG alteration; Upregulated Tom40 associated with heat stress-induced cardiomyocyte apoptosis; Reduced expression of Tom40 in hearts of old DCM patients. Here, TOMM40 is linked to cardiovascular disorder.