In the present manuscript, we show that (1) human PRNP gene expression is up-regulated by ER stress, (2) that the UPR-activated sXBP1 and ΔATF6α are involved in transcriptional activation of PRNP, (3) that PrP protects against ER stress-mediated cell death, and (4) that PrP may contribute to increased survival of breast cancers. The gene discussed is PRNP; the disease is breast cancer.