As the most invasive lysosomal cathepsin in GBM, CTSB remodels ECM to create prerequisite niches for invasion33 by degrading ECM components(such as laminin, collagen, fibrin, tenascin-C)42, triggering the uPA/plasminogen/plasmin proteolytic cascade42, activating other proteolytic enzyme systems32, releasing cytokines and growth factors, aggravating peritumoral edema and acidic microenvironment43. Here, CTSB is linked to glioblastoma.