Background：

The 78 kDa glucose regulated protein/BiP (GRP78) belongs to the family of ~70 kDa heat shock proteins (HSP 70). GRP78 is a resident protein of the endoplasmic reticulum (ER) and may associate transiently with a variety of newly synthesized secretory and membrane proteins or permanently with mutant or defective proteins that are incorrectly folded， thus preventing their export from the ER lumen. GRP78 is a highly conserved protein that is essential for cell viability. The highly conserved sequence Lys-Asp-Glu-Leu (KDEL) is present at the C terminus of GRP78 and other resident ER proteins including glucose regulated protein 94 (GRP 94) and protein disulfide isomerase (PDI). The presence of carboxy terminal KDEL appears to be necessary for retention and appears to be sufficient to reduce the secretion of proteins from the ER. This retention is reported to be mediated by a KDEL receptor.