Ctsk, encoding cathepsin K, is a cysteine protease. It has a strong activity in degrading extracellular matrix and is closely related to osteoclast-mediated bone destruction [1,3,4,5,6,7,8,9]. It may be involved in the IL-17 signaling pathway, as indicated by pathway enrichment analysis in castration-resistant prostate cancer (CRPC) research [1].

In a mouse model (Ctsk-Cre;Trp53f/f/Rb1f/f), ablation of Trp53/Rb1 in Ctsk-expressing cells led to spontaneous development of osteosarcoma, and inhibition of YAP/TAZ by verteporfin (VP) delayed osteosarcoma progression [2]. In the study of postmenopausal Chinese women, neither serum cathepsin K nor CTSK gene polymorphisms were correlated with bone mineral density (BMD) or bone turnover markers [3]. Mutations in the CTSK gene are responsible for pycnodysostosis, a rare autosomal recessive skeletal dysplasia, as shown in research on patients from different ethnic groups [4,5,6,7,8,9].

In conclusion, Ctsk is crucial for bone-related processes, especially those involving extracellular matrix degradation and osteoclast-mediated bone resorption. Mouse models, like the Ctsk-Cre;Trp53f/f/Rb1f/f mice, have been instrumental in revealing its role in osteosarcoma development. Understanding Ctsk's function is important for diseases such as pycnodysostosis and potentially for CRPC, where it may serve as a therapeutic target [1,2,4,5,6,7,8,9].