Presenilin-2 (PSEN2)

Presenilin-2 is a multi-pass transmembrane protein that serves as a catalytic core subunit of the gamma-secretase complex, an intramembrane protease essential for the regulated cleavage of a variety of proteins, most famously the amyloid precursor protein (APP) and the Notch receptor[1][2][4]. Mutations in the PSEN2 gene are causative for rare inherited forms of early-onset familial Alzheimer’s disease, owing to altered gamma-secretase activity and increased production of the pathogenic amyloid-beta 42 peptide[1][2][3]. Presenilin-2 is also involved in calcium signaling and membrane protein trafficking. It is a validated therapeutic target, but broad inhibition of gamma-secretase can cause significant side effects primarily due to disruption of Notch and other critical pathways[1][2][3].

Other names

PS2Presenilin 2PSEN2 protein

Inhibition of gamma-secretase activity to reduce amyloid-beta production Modulation of substrate cleavage (e.g. Notch, APP)