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BACE-1 is an aspartic protease and an integral membrane protein. BACE-1 is the peptidase predominantly responsible for cleavage of the amyloid precursor protein β site in the brain to generate the amyloid β peptide. Because the amyloid β peptide is a major component of amyloid plaques, BACE-1 has been implicated in the onset and/or progression of Alzheimer's disease. BACE-1 is expressed in a variety of human tissues. It is likely that this peptidase has functions in addition to its hydrolysis of the amyloid precursor protein. The peptidase activity of BACE-1 is optimal under mildly acidic conditions (pH 3.5 -5.5), consistent with its proposed function in an acidic intracellular compartment.