《生命科学》 2026, 38(3): 428-443
组织蛋白酶X在疾病中的新作用和治疗意义
摘 要：
组织蛋白酶X（cathepsin X，Cat X）是半胱氨酸组织蛋白酶家族的一员。它是一种溶酶体蛋白酶，只具备羧肽酶活性，不具备内肽酶活性，参与细胞黏附、细胞迁移与信号转导等多种生物学过程。此外，越来越多的证据表明，Cat X表达或活性失调可能导致多种疾病的发展。本综述旨在阐明Cat X蛋白质结构、底物特异性、抑制剂调控等生物学特性，并总结Cat X参与各种生理和病理过程的机制，进而探讨其作为创新治疗靶点的潜力和面临的挑战。
通讯作者：倪军军 , Email:nijunjun@bit.edu.cn
Abstract:
Cathepsin X (Cat X), a unique lysosomal cysteine protease encoded by the CTSZ gene, distinguishes itself through exclusive carboxypeptidase activity and a specialized protein architecture. Unlike other family members, Cat X possesses an exceptionally short propeptide, which facilitates non-proteolytic interactions with integrins alongside its traditional enzymatic functions. This review clarifies the molecular hallmarks of Cat X, emphasizing how its structural insertions dictate substrate specificity towards critical signaling molecules. Recent evidence underscores the pivotal role of Cat X dysregulation in driving the progression of various human pathologies. In neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, Cat X modulates neuroinflammation and neuronal survival by proteolytically inactivating neurotrophic factors or processing toxic protein fragments. Within the oncology landscape, Cat X promotes epithelial-mesenchymal transition, cell invasion, and tumor microenvironment remodeling across diverse malignancies, including glioblastoma and hepatocellular carcinoma. Beyond these, Cat X is implicated in autoimmune conditions and inflammatory fibrotic diseases. We further evaluate the development of small-molecule inhibitors, transitioning from irreversible probes like AMS36 to highly selective, reversible agents such as Compound 25, which demonstrate substantial therapeutic potential in preclinical models. By integrating structural biology with clinical pathology, this review positions Cat X as a versatile molecular hub. Ultimately, deciphering the upstream regulatory networks and the dynamic balance of Cat X activity between the central nervous system and peripheral circulation will be essential for validating Cat X as a robust diagnostic biomarker and a precision therapeutic target.
Communication Author：NI Jun-Jun , Email:nijunjun@bit.edu.cn
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