Cathepsin Z (CTSZ) (CTSZ)

Cathepsin Z, historically and frequently referred to as Cathepsin B2, is a lysosomal cysteine protease belonging to the papain (C1) family [5, 9, 15]. Unlike the related Cathepsin B, which acts as both an endopeptidase and a peptidyl-dipeptidase, Cathepsin Z functions strictly as a carboxypeptidase, removing single amino acids or dipeptides from the C-termini of protein substrates [9, 15, 19]. It is ubiquitously expressed in human tissues and plays a critical role in normal lysosomal protein turnover, as well as specialized functions in immune cell signaling and cell adhesion via a specialized RGD motif that binds to integrins [12, 15]. In pathological contexts, Cathepsin Z is notably overexpressed in various malignancies—including gastric, colorectal, and prostate cancers—where it facilitates tumor invasion and metastasis by remodeling the extracellular matrix [8, 13, 15]. It is also implicated in neurodegenerative disorders and inflammatory diseases, while its orthologs in parasites like Schistosoma are essential for host skin invasion [1, 3, 6, 12]. Although currently a subject of intense research for the development of small-molecule inhibitors like nitriles or vinyl sulfones, there are no FDA-approved drugs specifically targeting Cathepsin Z [10, 16, 20].

Other names

Cathepsin B2Cathepsin XCathepsin PCathepsin YCarboxypeptidase LBCTSZCTSXLysosomal carboxypeptidase B

Small-molecule inhibition of the cysteine-type carboxypeptidase activity by binding to the enzyme's catalytic active site, thereby preventing the degradation of terminal peptide bonds in target proteins and disrupting tumor invasion or parasite entry.