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Cathepsin S: molecular mechanisms in inflammatory and immunological processes

Huan Gao, Zirui Zhang, Jiayu Deng, Yanqing Song

2025Frontiers in Immunology22 citationsDOIOpen Access PDF

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.

Topics & Concepts

CathepsinInflammationCathepsin SCell biologyImmune systemProteostasisProteasesBiologyProteaseSignal transductionMatrix metalloproteinaseCysteine proteaseImmunologyChemistryEnzymeBiochemistryProtease and Inhibitor MechanismsOcular Diseases and Behçet’s SyndromeSignaling Pathways in Disease
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