Gamma-secretase is a membrane protein complex with unusual aspartyl protease 
activity that cleaves a variety of type I transmembrane proteins, such as APP, 
Notch and E-cadherin, within their transmembranous regions. Gamma-secretase was 
first recognized because of its role in the production of Abeta peptides that 
are pathogenic in Alzheimer's disease. There is overwhelming evidence 
demonstrating that four components, presenilin, nicastrin, APH-1 and PEN-2, are 
necessary and sufficient for gamma-secretase activity. However, based on the 
findings of studies conducted on cells overexpressing these four components, the 
existence of regulatory components of the gamma-secretase complex has been 
postulated. Recently, an additional subunit of the gamma-secretase complex, 
membrane protein CD147, has been identified through the purification and 
characterization of endogenous complexes from HeLa cell membranes. Removal of 
CD147 from gamma-secretase complexes increases the production of Abeta-peptides. 
Elucidating the molecular mechanism by which CD147 exerts its effect on the 
activity of the gamma-secretase complex will help us to further understand the 
pathogenesis of Alzheimer's disease, and may allow for the development of novel 
therapeutics.