Cardiac and renal diseases(CRDs)are characterized by extensive remodeling of the extracellular matrix(ECM)architecture of the cardiorenal system.Among the many extracellular proteolytic enzymes present in cardiorenal cells and involved in ECM remodeling,members of the matrix metalloproteinase family and serine protease family have received the most attention.However,recent findings from laboratory and clinical studies have indicated that cysteine protease cathepsins also participate in pathogenesis of the heart and kidney.Deficiency and pharmacological inhibition of cathepsins have allowed their in vivo evaluation in the setting of pathological conditions.Furthermore,recent studies evaluating the feasibility of cathepsins as a diagnostic tool have suggested that the serum levels of cathepsins L,S and K and their endogenous inhibitor cystatin C have predictive value as biomarkers in patients with coronary artery disease and heart and renal failure.The goal of this review is to highlight recent discoveries regarding the contributions of cathepsins in CRDs,particularly hypertensive heart failure and proteinuric kidney disease.