Recently, mounting evidence has demonstrated that dysregulation of Ca2+ transfer from the ER to mitochondria by the IP3R-Grp75-VDAC1-MCU axis, located at sites of ER-mitochondria coupling, will lead to mitochondrial Ca2+ overload, opening of mitochondrial permeability transition pore, the release of pro-apoptotic factors such as cytochrome c, caspase activation, and apoptosis in many different cells and diseases including neurodegeneration, metabolic diseases, and cancer [4–8]. Here, CYCS is linked to cancer.