Heart failure is a debilitating condition affecting an increasing fraction of the population and often leads to the requirement for a transplant. In this study, we will clarify some of the underlying mechanisms by investigating function and internal structure of cells from failing patient hearts. We hypothesize that changes in the smallest internal cell structures may be responsible for a much weaker contraction. We have identified a protein that is progressively lost in heart failure and we will test if a therapy to prevent the loss of this protein (called junctophilin) can prevent the weakening of the heart. Using an experimental model of heart failure, the experiments in this study will improve our understanding of how and why heart failure develops in some patients and will test the prospect of a new treatment approach to improve the health of affected individuals.