The three dimensional structure of many extracellular proteins is stabilized by the formation of disulphide bonds. Studies suggest that a microsomal enzyme known as Protein Disulphide-Isomerase (PDI) is involved in disulphide-bond formation and isomerization, as well as the reduction of disulphide bonds in proteins. PDI, which catalyses disulphide interchange between thiols and protein dilsulphides, has also been referred to as thiol:protein-disulphide oxidoreductase and as glutathione:insulin transhydrogenase because of its role in reduction of disulphide bonds. The highly conserved sequence Lys-Asp-Glu-Leu (KDEL) is present at the carboxy-terminus of PDI and other soluble endoplasmic reticulum (ER) resident proteins including the 78 and 94 kDa glucose regulated proteins (GRP78 and GRP94 respectively). The presence of carboxy-terminal KDEL appears to be necessary for ER 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.