Remarkably, in addition to the ER residents, substantial evidence have indicated that PDIs translocate to extra ER locations such as the cell surface and possibly cytosol and participate in cellular activities such as agonist-triggered NADPH oxidase (Nox) activation, cell migration in vascular cells and macrophages, expansive caliber remodeling during injury repair, and the induction of HIV infection (37); however, how the subcellular PDIs translocation occurs and if these external ER PDIs play roles in cancer development remain unclear. The gene discussed is FMO5; the disease is cancer.