Treatment with rapamycin, an mTOR inhibitor, activates autophagy, promotes SERCA activity via the phosphorylation phospholamban (PLB) by CAMKII, and enhances the expressions of mitochondrial respiratory complex proteins via prompting TFEB‐PGC1α pathway, effectively alleviating heart failure induced by STX12 deficiency. This evidence concerns the gene CAMK2G and heart failure.