Neprilysin/CD10(NEP) is a zinc metallopeptidase expressed at the cell surface of a variety of cells. The functions is both as an endopeptidase with a thermolysin-like specificity and as a dipeptidyl-carboxypeptidase. NEP has been shown to be involved in the degradation of enkephalins in the mammalian brain and the inactivation of circulating atrial natriuretic peptide. NEP has also been identified as the common acute lymphocytic leukemia antigen (CALLA), and is expressed on the surface of lymphocytes in some disease states. These and other observations have resulted in considerable interest in NEP as a target for analgesics and antihypertensive drugs. NEP is also a major degrading enzyme of amyloid β peptide (Aβ) in the brain, indicating that down-regulation of NEP activity, which could be caused by aging, can contribute to the development of Alzheimer’s disease by promoting Aβ accumulation.