In response to environment stimuli, the PALs are delivered to the vacuole, another plant organelle, where the acidic environment triggers autocatalytic removal of the cap domain for enzyme activation (Fig. 2A).17 Similarly, the mammalian counterparts, known as legumain and recognized as targets in cancer therapy, reside in the ER and become activated under specific conditions.23,24 This organization ensures that only substrates with the appropriate localization sequences can access these organelles and undergo modifications only when PALs are activated. Here, CTSC is linked to cancer.