Ctsh, short for cathepsin H, is a lysosomal cysteine protease with unique aminopeptidase activity. It is widely expressed in multiple organs such as the lung, pancreas, and brain. Ctsh is involved in regulating biological behaviors of cancer cells and pathological processes in brain diseases, and is expected to be active in extra-lysosomal and extracellular spaces due to its optimal activity at neutral pH [4].

In bladder cancer, multi-omics analyses showed that Ctsh is correlated with chemoresistance and semi-squamatization. Inhibition of cathepsin by E64 treatment, which targets Ctsh, induces full squamous differentiation and pyroptosis, specifically restraining chemoresistant muscle-invasive bladder cancers (MIBCs) [1].

In type 1 diabetes (T1D), the T allele of rs3825932 was associated with lower Ctsh expression. Overexpression of Ctsh protected insulin-secreting cells against cytokine-induced apoptosis, and the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients [3].

In thyroid carcinoma, high Ctsh mRNA expression was observed, which was conducive to the overall survival of patients, and Ctsh was determined as an independent prognostic factor [2].

In conclusion, Ctsh plays crucial roles in various diseases. In cancer, it is related to chemoresistance and prognosis; in T1D, it is involved in regulating β-cell function and disease progression. The study of Ctsh using different experimental models helps to understand the underlying mechanisms of these diseases, providing potential therapeutic strategies.