Presenilins associated rhombiod-like protein (PARL) is a mitochondrial intramembrane-cleaving protease belonging to the S54 family of proteins. PARL is involved in intramembrane regulated proteolysis as its catalytic activity involves the cleaving of signaling proteins at intracellular membranes to release active fragments in signal transduction cascades. Using a triad of histidine, serine and asparagine, PARL cleaves type-1 transmembrane domains. PARL is a multi-pass membrane protein localizing to the inner and outer mitochondrial membranes, but it can also be detected in the nucleus following proteolytical processing of P-β. PARL co-localizes with the presenilins PSEN1 and PSEN2, the familial Alzheimer disease products.