Cathepsin K

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Cathepsin K
Cathepsin K 1TU6.png
Ribbon diagram of cathepsin K, colored by secondary structure. From PDB: 1TU6​.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM601105 MGI107823 HomoloGene68053 ChEMBL: 268 GeneCards: CTSK Gene
EC number
RNA expression pattern
PBB GE CTSK 202450 s at tn.png
More reference expression data
Species Human Mouse
Entrez 1513 13038
Ensembl ENSG00000143387 ENSMUSG00000028111
UniProt P43235 P55097
RefSeq (mRNA) NM_000396 NM_007802
RefSeq (protein) NP_000387 NP_031828
Location (UCSC) Chr 1:
150.8 – 150.81 Mb
Chr 3:
95.5 – 95.51 Mb
PubMed search [1] [2]

Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene.[1][2]


The protein encoded by this gene is a lysosomal cysteine protease involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is expressed predominantly in osteoclasts.

Cathepsin K is a protease, which is defined by its high specificity for kinins, that is involved in bone resorption. The enzyme's ability to catabolize elastin, collagen, and gelatin allow it to break down bone and cartilage. This catabolic activity is also partially responsible for the loss of lung elasticity and recoil in emphysema. Cathepsin K inhibitors, such as odanacatib, show great potential in the treatment of osteoporosis. Cathepsin K is degraded by Cathepsin S, called Controlled Cathepsin Cannibalism.

Cathepsin K expression is stimulated by inflammatory cytokines that are released after tissue injury.

Clinical significance[edit]

Cathepsin K is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature.

Merck has a Cathepsin K inhibitor in Phase 3 clinical trials by the name of Odanacatib for an expected indication of osteoporosis. Velcura Therapeutics, Inc. has also developded a highly selective cathepsin K inhibitor named VEL-0230 and has been tested in human, rat, equine clinical trials. [3] [4] [5]


  1. ^ "Entrez Gene: CTSK cathepsin K". 
  2. ^ Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T (January 1995). "Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone". Biochem. Biophys. Res. Commun. 206 (1): 89–96. doi:10.1006/bbrc.1995.1013. PMID 7818555. 
  3. ^
  4. ^ Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H,. (2008). Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science, 319(5863), 624-627.
  5. ^ Hussein, H., Ishihara, A., Menendez, M., & Bertone, A. (2014). Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses. Journal of veterinary pharmacology and therapeutics.

Further reading[edit]

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