AUTHOR=Gao Huan , Zhang Zirui , Deng Jiayu , Song Yanqing 

TITLE=Cathepsin S: molecular mechanisms in inflammatory and immunological processes

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1600206

DOI=10.3389/fimmu.2025.1600206

ISSN=1664-3224

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.