On the other hand, cathepsins can be secreted out of the cells, in particular in cancer cells.22 A study recently found that extracellular release of cathepsin L in HER2 low breast cancer cells enables cleavage of T-DXds linker and subsequent payload release.28 This T-DXd-dependent cytotoxicity is not related to cellular uptake and would therefore not be reliant on the quantity of antigen expression on the cell surface. Here, CTSS is linked to cancer.