The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Abstract

Cathepsins are the most abundant lysosomal proteases that are mainly found in acidicendo/lysosomal compartments where they play a vital role in intracellular protein degradation,energy metabolism, and immune responses among a host of other functions. The discovery thatcathepsins are secreted and remain functionally active outside of the lysosome has caused a paradigmshift. Contemporary research has unraveled many versatile functions of cathepsins in extralysosomallocations including cytosol and extracellular space. Nevertheless, extracellular cathepsins are majorlyupregulated in pathological states and are implicated in a wide range of diseases including cancerand cardiovascular diseases. Taking advantage of the dierential expression of the cathepsinsduring pathological conditions, much research is focused on using cathepsins as diagnostic markersand therapeutic targets. A tailored therapeutic approach using selective cathepsin inhibitors isconstantly emerging to be safe and ecient. Moreover, recent development of proteomic-basedapproaches for the identification of novel physiological substrates oers a major opportunity tounderstand the mechanism of cathepsin action. In this review, we summarize the available evidenceregarding the role of cathepsins in health and disease, discuss their potential as biomarkers ofdisease progression, and shed light on the potential of extracellular cathepsin inhibitors as safetherapeutic tools.