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Presenilin-1 (PSEN1) is the catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins. Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1 and PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Presenilins are also involved in the cleavage of the Notch receptor, either by regulating gamma-secretase activity or by direct proteolytic activity. Three alternative splice variants of PSEN1 have been identified. Defects in PSEN1 are a cause of familial early-onset Alzheimer disease type 3, the most severe form of the disease.