Restored SERCA2 expression, which improves sarcoplasmic reticulum loading and excitation-contraction coupling, has been proposed as an approach to improve the systolic dysfunction in HFrEF, and gene therapy trials are now under way to test the improvement provided by directly increasing expression of SERCA2a in heart failure (ClinicalTrials.gov ID NCT04703842 and NCT06061549). This evidence concerns the gene ATP2A2 and heart failure.