Provided are methods of treating or preventing Ca2+/calmodulin-dependent kinase II (CaMKII)-mediated diseases, methods of alleviating cardiac injury, methods of stimulating the activity of ubiquitin-conjugating enzyme, methods of preventing degradation of ubiquitin-conjugating enzyme, methods of preventing cardiomyocyte death, methods of reducing DNA damage in a cell, methods for diagnosing CaMKII-mediated diseases, kits for diagnosing CaMKII-mediated diseases, biomarkers for diagnosing a CaMKII-mediated disease, and use of CaMKIIδ9 as a biomarker for diagnosing a CaMKII-mediated disease. Also provided herein are methods for identifying molecules, isolated polypeptides, isolated nucleic acids, and antagonists thereof.