A major cause of cardiac dysfunction is the disruption of the coordinated calcium signalling pathways within the cells of the heart. A protein pivotal in regulating cardiac cell calcium signalling is RyR2. The function of RyR2 is in turn regulated by two cell signalling proteins known as kinases. Interestingly, both kinases lead to an increase in RyR2 function which can ultimately cause disease. Therefore, they are the focus of many drug studies aimed at reducing arrhythmias and cardiomyopathies. Excitingly, we have recently identified a third kinase which, unlike those previously identified, reduces the function of RyR2 and may therefore be protective against disease. We will examine the effect of modulating this kinase on cardiac dysfunction and determine the level to which its activity is altered in patients with cardiac disease. This work is critical for identifying new targets for the next generation of cardio-protective drugs which are urgently required.