Cysteine cathepsins are a group of closely related proteolytic enzymes active at low pH. The most well-studied function of these enzymes is protein degradation within lysosomes. However, accumulating evidence suggests that cysteine cathepsins also function at physiological pH levels in other cellular compartments outside lysosomes, as well as in the extracellular space. Many of these extra-lysosomal functions of cysteine cathepsins are typically associated with pathological processes, contributing to conditions such as oncogenesis and metastasis, neurodegenerative diseases, cardiovascular disorders, and autoimmune and inflammatory processes. Consequently, cysteine cathepsins have been proposed as diagnostic and prognostic molecular markers, as well as pharmacological targets. Notably, the pathological processes involving these enzymes often operate independently of their classical lysosomal functions. This work aims to outline key questions, the answers to which could enhance our understanding of the fundamental mechanisms governing the extra-lysosomal functions of cysteine cathepsins. Addressing these questions is also critical for developing novel therapeutic strategies to treat diseases in which cysteine cathepsins play a pathogenic role.
Andrey A. Zamyatnin (Wed,) studied this question.