Our recent discovery that GRP78, a key stress-inducible ER luminal chaperone, commonly overexpressed in cancer cells and cells that have acquired therapeutic resistance, is prominently expressed in the nucleus of a wide variety of cancer cells where it acts as a transcriptional regulator allowing cells to adopt an invasive phenotype represents a paradigm shift about its role in regulating homeostasis and tumorigenesis (17). Here, HSPA5 is linked to cancer.