Researchers speculated that under cancer-related stress, as the plasma membrane originates from ER membrane, the ER membrane-spanned subpopulation of GRP78 transduces to the cell surface, interacts with other cell-surface proteins like glycosylphosphatidylinositol-anchored proteins, and preferentially exists as peripheral protein on the plasma membrane, which is never or rarely observed in normal cells [22]. This evidence concerns the gene HSPA5 and cancer.