The endoplasmic reticulum is part of a protein sorting pathway, or in essence, the transportation system of the eukaryotic cell. The majority of endoplasmic reticulum resident proteins are retained in the endoplasmic reticulum through a retention motif. This motif is composed of four amino acids at the C-terminal end of the protein sequence. The most common retention sequence is KDEL (lys-asp-glu-leu). Grp78 and Grp94 and PDI all share the C-terminal KDEL sequence. 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.