Murine models with conditional deletion of Grp78 and phosphatase and tensin homolog (Pten)—a tumor suppressor that antagonizes PI3K—demonstrate that GRP78 is required for the full activation of PI3K–AKT signaling, highlighting its role as a co-factor in prostate tumorigenesis and leukemogenesis. This evidence concerns the gene HSPA5 and neoplasm.