Diseases, such as multiple myeloma, a cancer of highly secretory plasma cells where the UPR is thought to play a major cytoprotective role (Carrasco et al., 2007; Leung-Hagesteijn et al., 2013), or triple-negative breast cancer, in which high XBP1 activity has been correlated with poor patient prognosis (Chen et al., 2014), have exposed the potential significance of targeting the UPR in cancers. The gene discussed is XBP1; the disease is AL amyloidosis.