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Among stimulus\u2010responsive approaches, enzyme\u2010triggered activation has emerged as a particularly attractive method because it can couple drug release to disease\u2010associated biochemical activity. Cathepsins, a family of lysosomal proteases including 15 types, implicated in cancer, inflammation, and other pathological processes, have become important enzymatic triggers in this area. Most cathepsin\u2010responsive systems focused on cathepsin B, whose elevated activity in tumors and favorable intracellular localization have supported the development of peptide\u2010cleavable prodrugs, from small\u2010molecule prodrugs to various drug conjugates. More recent studies have extended this concept beyond cathepsin B to other cathepsins such as L, E, and S, highlighting a shift toward substrate\u2010selective design and improved biological precision. 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