Lysosomal cathepsin (CTS) (CTS)

Lysosomal cathepsins are a family of proteases, predominantly cysteine proteases, that function within the acidic environment of lysosomes to degrade and recycle intracellular and endocytosed proteins (Stoka et al., 2016). While they are essential for cellular homeostasis, specific members of the family play specialized roles, such as Cathepsin K in bone resorption and Cathepsin S in MHC class II-mediated antigen presentation (Yadati et al., 2020). In diseases like cancer, cathepsins are often upregulated and secreted into the extracellular matrix, where they facilitate tumor invasion and metastasis by degrading structural proteins (Olson & Joyce, 2015). They also serve as critical host factors for the entry of several viruses, including Ebola and SARS-CoV-2, by processing viral glycoproteins (Bojkova et al., 2020). Therapeutic strategies have focused on small-molecule inhibitors to treat osteoporosis, inflammatory disorders, and malignancies, though achieving selectivity remains a significant hurdle due to the high structural similarity among family members (Vizovisek et al., 2019). Clinical development of some inhibitors, such as the Cathepsin K inhibitor Odanacatib, was halted due to safety concerns including an increased risk of stroke and skin-related adverse events (Mullard, 2016).

Other names

Cathepsin familyLysosomal proteaseLysosomal cysteine proteaseCysteine cathepsinAspartic cathepsin

Small-molecule inhibition of the proteolytic activity of specific cathepsin enzymes to prevent substrate degradation or viral processing (Yadati et al., 2020).