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. The gene discussed is PLN; the disease is heart failure.