Cystatin S (CST4)

Cystatin S is a secretory protein from the type 2 cystatin family, encoded by the CST4 gene, with strong inhibitory activity against specific cysteine proteases such as papain and ficin[2]. It is abundantly present in human saliva, tears, and seminal plasma, contributing to the regulation of proteolytic activity and thus providing tissue protection in these fluids. In the ocular environment, it maintains tear film stability and resists protease-driven tissue damage[1]. In cancer, CST4 is implicated in tumor progression and metastasis, and elevated serum CST4 serves as a prognostic biomarker, particularly in gastric and colorectal cancers[3]. Additionally, CST4 is involved in modulating the tumor microenvironment, likely by influencing immune responses through signaling pathways including TGF-β. Its diagnostic and prognostic applicability has been investigated, but there are currently no drugs targeting CST4 directly[1][2][3].

Other names

Cystatin-SCST4Cystatin-4Cystatin-SA-IIISalivary acidic protein 1cystatin 4cystatin-SA-IIIsalivary acidic protein 1

Inhibition of cysteine protease activity: CST4 reduces activity of proteolytic enzymes, thereby protecting tissue integrity. Tumor progression: CST4 overexpression promotes invasiveness via pathways such as ELFN2, VEGF-MAPK/ERK-MMP9/2. Immune modulation: Alters the tumor microenvironment and immune cell infiltration through TGF-β pathway interactions.