The endoplasmic reticulum exerts a quality control over newly synthesized proteins and a variety of components have been implicated in the specific recognition of aberrant or misfolded polypeptides. Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. SPP is required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides, and may play a role in graft rejection. It also may be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein.