GRP78 is up-regulated in many cancers and is associated with poor survival.[9-11] However, when cells are unable to protect against ER stress, both intrinsic and extrinsic cell death pathways are activated, and severely damaged cells are removed.[12, 13] Additionally, after these sensor molecules (IRE1α/XBP-1, ATF6, and PERK) are released from GRP78, cascades of UPR signaling are activated to balance survival against damage caused by ER stress. The gene discussed is HSPA5; the disease is cancer.