CaMKII is a newly identified RIP3 substrate that helps delineate a RIP3-CaMKII-mitochondrial permeability transition pore (mPTP) myocardial necroptosis pathway, a potential therapeutic target for ischemia- and oxidative stress-induced myocardial injury and heart failure (Zhang et al., 2016). The gene discussed is RIPK3; the disease is heart failure.