A plethora of cancer-relevant proteins controls metabolic MERC signaling,including p53 (Giorgi et al., 2015), PTEN (Bononi et al., 2013), thekinase Akt (Betzet al., 2013), breast/ovarian cancer susceptibility gene1 (BRCA1) (Hedgepeth et al., 2015) and the promyelocytic leukemia(PML) protein (Giorgi et al., 2010; Missiroli et al., 2016).PML is very sensitive to oxidation (Tessier et al., 2017).While its MERC activity increases IP3R-mediatedCa2+ flux towards mitochondria, in its absence ROSincrease (Niwa-Kawakita et al., 2017). The gene discussed is PTEN; the disease is cancer.