In previous reports regarding the mechanism of action of BTZ-induced cancer cell apoptosis, accumulation of misfolded proteins followed by fatal ER stress,16, 32 inactivation of the nuclear factor-κB pathway,33 mitochondrial membrane injury facilitated by BH3-only proteins, including Noxa, Bid, puma and Bik, and cleaved Mcl-1 isoform, all seemed indispensable.13, 34, 35, 36 However, little was known about how prolonged ER stress activates these pro-apoptotic factors. The gene discussed is BID; the disease is cancer.