Neprilysin is a neutral endopeptidase that cleave peptides. It inactivates several peptides including natriuretic peptides, endothelin, bradykinins, Ang II and beta-amyloid among others. Inhibition of neprilysin with the drug sacubitril in combination with renin angiotensin system blockade (valsartan) in chronic heart failure was reported recently in NEJM (PARADIGM-HF). This trial studied LCZ696 (sacubitril+valsartan) versus enalapril in ~8000 patients with chronic heart failure. The study was stopped early secondary to overwhelming benefit in the LCZ696 arm. Studies are currently underway looking at neprilysin blockade in proteinuric CKD.