Cathepsin S: molecular mechanisms in inflammatory and immunological processes

  • Front Immunol. 2025 Jul 7:16:1600206. doi: 10.3389/fimmu.2025.1600206.
Huan Gao  1  2 ,  Zirui Zhang  1 ,  Jiayu Deng  3 ,  Yanqing Song  1  3
Affiliations
  • 1. College of Pharmacy, Jilin University, Changchun, Changchun, China.
  • 2. Department of Clinical Pharmacy, the First Hospital of Jilin University, Changchun, China.
  • 3. Department of Pharmacy, Lequn Branch, the First Hospital of Jilin University, Changchun, China.
PMID: 40692794 DOI: 10.3389/fimmu.2025.1600206
Abstract

Cathepsin S (CTSS), a lysosomal cysteine Protease predominantly expressed in immune cells, governs inflammatory and immunological cascades through proteolytic activity. Beyond maintaining lysosomal proteostasis through protein degradation, CTSS executes dual immunomodulatory functions: intracellularly processing antigen-presenting molecules and modulating inflammatory signaling cascades; extracellularly activating protease-activated receptors (PARs) and remodeling the extracellular matrix (ECM). Its dysregulation drives pathology in autoimmune disorders, chronic inflammation, and neoplasia, establishing CTSS as a multifaceted therapeutic target. This review comprehensively explores the contributions of CTSS signaling in immune-mediated inflammatory diseases, critically evaluates its therapeutic potential, highlighting its significance in the development of innovative treatment strategies.

Keywords
cathepsin S (CTSS); immunoregulation; inflammatory disease; molecular mechanism; therapeutic targets.
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