Cathepsins in the extracellular space: Focusing on non-lysosomal proteolytic functions with clinical implications

Cathepsins can be found in the extracellular space, cytoplasm, and nucleus. It was initially suspected that the primary physiological function of the cathepsins was to break down intracellular protein, and that they also had a role in pathological processes including inflammation and apoptosis. However, the many actions of cathepsins outside the cell and their complicated biological impacts have garnered much interest. Cathepsins play significant roles in a number of illnesses by regulating parenchymal cell proliferation, cell migration, viral invasion, inflammation, and immunological responses through extracellular matrix remodeling, signaling disruption, leukocyte recruitment, and cell adhesion. In this review, we outline the physiological roles of cathepsins in the extracellular space, the crucial pathological functions performed by cathepsins in illnesses, and the recent breakthroughs in the detection and therapy of specific inhibitors and fluorescent probes in associated dysfunction. •This review focuses on cathepsin synthesis, extracellular matrix remodeling, antigen presentation, and clinical implications of cathepsins in the extracellular space.