Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD, MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1, MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP, MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).Synonyms: Gamma-secretase-activating protein, Protein pigeon homolog