Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimer’s disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligo-nucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-aconverting enzyme (TACE;ADAM17) in theectodomainsheddingofACEand APP from human SH-SY5Y cells.