ER stress inducers are known to activate the extrinsic apoptotic pathway through the PERK-mediated induction of the CHOP transcription factor, leading to the upregulation of TRAILR2/DR5 expression and TRAIL-independent intracellular clustering and activation of TRAIL-R2/DR5 in tumor cells [13–15]. The gene discussed is TNFRSF10B; the disease is neoplasm.