H13 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. It is required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides. Involved in the intramembrane cleavage of the integral membrane protein PSEN1 By similarity. It may play a role in graft rejection.