Therapeutic potential of targeting cathepsin S in pulmonary fibrosis

Young Jo Yoo, Eun Choi, Yejin Kim, Yunyoung Cha, Eunhye Um, Younghwa Kim, Yunji Kim, Yun Sil Lee

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


Cathepsin S (CTSS), a lysosomal protease, belongs to a family of cysteine cathepsin proteases that promote degradation of damaged proteins in the endolysosomal pathway. Aberrant CTSS expression and regulation are associated with the pathogenesis of several diseases, including lung diseases. CTSS overexpression causes a variety of pathological processes, including pulmonary fibrosis, with increased CTSS secretion and accelerated extracellular matrix remodeling. Compared to many other cysteine cathepsin family members, CTSS has unique features that it presents limited tissue expression and retains its enzymatic activity at a neutral pH, suggesting its decisive involvement in disease microenvironments. In this review, we investigated the role of CTSS in lung disease, exploring recent studies that have indicated that CTSS mediates fibrosis in unique ways, along with its structure, substrates, and distinct regulation. We also outlined examples of CTSS inhibitors in clinical and preclinical development and proposed CTSS as a potential therapeutic target for pulmonary fibrosis.

Original languageEnglish
Article number112245
JournalBiomedicine and Pharmacotherapy
StatePublished - Jan 2022

Bibliographical note

Publisher Copyright:
© 2021 The Authors


  • Cathepsin S
  • Clinical and preclinical
  • Inhibitors
  • Pulmonary fibrosis
  • Therapeutic target


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