[6][7][8] Although only recently discovered, intramembrane proteases are of significant research interest because of their major biological functions and their relevance to human disease.
[5][17] Their active sites are located within the transmembrane helices and form an aqueous environment within the hydrophobic lipid bilayer.
Most intramembrane proteases are thought to function as monomers, with the notable exception of presenilin which is active only in the gamma-secretase protein complex.
[17] Three of the four groups of intramembrane proteases cleave their substrates within transmembrane domains and the scissile bond is located inside the membrane.
[21][18] Intramembrane proteolysis was proposed in the 1990s by researchers studying Alzheimer's disease, such as Dennis Selkoe, as a possible mechanism for the processing of amyloid precursor protein.