{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:40:57Z","timestamp":1785426057025,"version":"3.56.0"},"reference-count":103,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016971","name":"Lomonosov Moscow State University","doi-asserted-by":"crossref","award":["123063000002-7"],"award-info":[{"award-number":["123063000002-7"]}],"id":[{"id":"10.13039\/501100016971","id-type":"DOI","asserted-by":"crossref"}]},{"award":["123063000002-7"],"award-info":[{"award-number":["123063000002-7"]}],"id":[{"id":"https:\/\/ror.org\/010pmpe69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004285","name":"St. Petersburg State University","doi-asserted-by":"crossref","award":["125021902561-6"],"award-info":[{"award-number":["125021902561-6"]}],"id":[{"id":"10.13039\/501100004285","id-type":"DOI","asserted-by":"crossref"}]},{"award":["125021902561-6"],"award-info":[{"award-number":["125021902561-6"]}],"id":[{"id":"https:\/\/ror.org\/023znxa73","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Federal Territory \u201cSirius\u201d","award":["22-03"],"award-info":[{"award-number":["22-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms27115061","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"5061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cathepsin Z\/X: Breaking Down the Known and Unknown"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5825-5570","authenticated-orcid":false,"given":"Kristina","family":"Zdravkova","sequence":"first","affiliation":[{"name":"AD Alkaloid Skopje, Boulevard Alexander the Great 12, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Pavicevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences, Faculty of Forensic Sciences and Engineering, University of Criminal Investigation and Police Studies, Cara Dusana 196, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olja","family":"Mijanovi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-118X","authenticated-orcid":false,"given":"Ana","family":"Brankovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Forensic Sciences, Faculty of Forensic Sciences and Engineering, University of Criminal Investigation and Police Studies, Cara Dusana 196, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5825-0032","authenticated-orcid":false,"given":"Polina M.","family":"Ilicheva","sequence":"additional","affiliation":[{"name":"Institute of 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Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-2006","authenticated-orcid":false,"given":"Aleksandr A.","family":"Rubel","sequence":"additional","affiliation":[{"name":"Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-4288","authenticated-orcid":false,"given":"Ivan V.","family":"Rodionov","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Department of Biological Chemistry, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila V.","family":"Savvateeva","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-6545","authenticated-orcid":false,"given":"Alessandro","family":"Parodi","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Scientific Center for Translation Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-4565","authenticated-orcid":false,"suffix":"Jr.","given":"Andrey A.","family":"Zamyatnin","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12648","DOI":"10.1021\/bi991371z","article-title":"Human Cathepsin X: A Cysteine Protease with Unique Carboxypeptidase Activity","volume":"38","author":"Zhang","year":"1999","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.semcancer.2025.04.001","article-title":"Cathepsins: Emerging Targets in the Tumor Ecosystem to Overcome Cancers","volume":"112","author":"Fujii","year":"2025","journal-title":"Semin. 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