Signal sequences are required for translocating secretory and membrane proteins into the endoplasmic reticulum (ER). At the ER membrane, the signal peptidase complex (SPC) cleaves off signal peptides before releasing the proteins to their destination. The SPC comprises four subunits in yeast and Drosophila, and five subunits in mammals - Sec11p/twr is the single catalytic subunit in yeast/flies, whereas 2 homologous subunits, SEC11A (aka SPC18) and SEC11C (aka SPC21) have catalytic activity in the mammalian complex. (Adapted from PMID:29265467.)