Signal peptide peptidase-like 2a (MEROPS identifier A22.007) is an intramembrane peptidase that performs regulated intramembrane proteolysis, particularly on single pass type II transmembrane proteins. It is predominantly localized to late endosomes and lysosomes because of a C-terminal tyrosine motif []. SPPL2a cleaves the N-terminal fragment of the invariant chain, and is essential for B-cell development []. The membrane stump, following shedding of the ectodomain, of frontotemporal lobar degeneration risk factor TMEM106B is also a substrate [].
