Cathepsin Z/X: Breaking Down the Known and Unknown
Authors:
- Kristina ZdravkovaKZKristina Zdravkova
- Milena PavicevićMPMilena Pavicević
- Olja MijanovićOMOlja Mijanović
- Ana BrankovićAna Branković
- Polina M. IlichevaPIPolina M. Ilicheva
- Aleksandra StankovskiASAleksandra Stankovski
- Jelena KaranovićJKJelena Karanović
- Dusan PualićDPDusan Pualić
- Aleksandr A. RubelARAleksandr A. Rubel
- Ivan V. RodionovIRIvan V. Rodionov
- Lyudmila V. SavvateevaLSLyudmila V. Savvateeva
- Alessandro ParodiAlessandro Parodi
Open Access
- 3 June 2026
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 27 (11) , 5061
Abstract
Cathepsin Z/X (Cat Z/X) is a distinct member of the cysteine cathepsin family, known for its distinctive structural and functional properties, such as strict carboxypeptidase activity and integrin-binding motifs. These features set Cat Z/X apart from other cysteine proteases and underlie its involvement in diverse physiological and pathological processes, including immune regulation, cell signaling, and extracellular matrix remodeling. Dysregulated Cat Z/X expression and activity have been associated with various diseases, including cancer, neurodegenerative disorders, and metabolic conditions. This review summarizes current knowledge on Cat Z/X, focusing on its structural characteristics, biological functions, and roles in disease pathogenesis, particularly in malignancies, neuroinflammation, and metabolic disorders. It also explores natural and synthetic Cat Z/X inhibitors and their potential for therapeutic development. Despite growing research interest, the precise molecular mechanisms and context-specific functions of Cat Z/X are not yet fully understood. Further research is required to elucidate its regulatory networks, refine detection methods, and develop selective modulators targeting its proteolytic and non-proteolytic activities. A deeper understanding of Cat Z/X biology could pave the way for its application as a diagnostic biomarker and therapeutic target in numerous diseases.Keywords
Funding Information
- Lomonosov Moscow State University (123063000002-7)
- Saint Petersburg State University (125021902561-6)
- Federal Territory “Sirius” (22-03)
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