Cystatin A (CSTA)

Cystatin A (CSTA) is a small (~11 kDa) single-domain cysteine protease inhibitor of the type 1 cystatin (stefin) family, primarily expressed in epithelial and lymphoid tissues[1][4][5]. It tightly inhibits the lysosomal cysteine proteases cathepsins B, H, and L[1][4]. Cystatin A is a precursor structural protein of the cornified envelope in keratinocytes and is crucial for epidermal development, cell–cell adhesion, and maintenance of the skin barrier[1][5]. Mutations or loss of function result in severe hereditary skin diseases (exfoliative ichthyosis, acral peeling skin syndrome)[1]. Polymorphisms are implicated in atopic dermatitis and other barrier dysfunctions[1][5]. Aberrant CSTA expression and function are linked to cancer progression, particularly in carcinomas where it serves as a prognostic biomarker; it modulates tumor invasion, migration, EMT/MET transitions, and response to anti-cancer agents by regulating protease activity and key signaling pathways such as MAPK and AKT[1][3].

Other names

AREISTF1STFAPSS4stefin ACystatin-ASCystatin ASStefin-Acystatin A (stefin A)N-terminally processed cystatin-Acystatin-A

Inhibition of cysteine proteases: Tight binding to cathepsins B, H, and L, and papain; Suppression of epithelial–mesenchymal transition (EMT) and promotion of mesenchymal–epithelial transition (MET) via inhibition of MAPK and AKT signaling; modulation of TGF-β1-induced EMT