PRSS8

PRSS8 is a human gene encoding prostasin, a highly conserved, extracellular, trypsin-like serine protease. Also known as channel-activating protease 1 (CAP1), prostasin is synthesized as an inactive zymogen and becomes catalytically active after proteolytic removal of an N-terminal activation peptide. In many tissues it is attached to the cell surface or secreted into luminal fluids.

Expression and localization: PRSS8 transcripts are abundant in epithelial tissues, including the kidney, lung, gastrointestinal tract, skin, and reproductive tract. The protein localizes primarily at the apical surface of epithelial cells and in some contexts can be found in luminal secretions.

Function: Prostasin participates in proteolytic cascades that regulate epithelial homeostasis. A key function is the proteolytic activation of the epithelial sodium channel (ENaC) by cleaving its gamma-subunit, thereby increasing channel activity and sodium absorption. Prostasin is part of a broader serine protease cascade with matriptase (ST14), which activates prostasin by proteolytic processing, enabling downstream proteolysis events. Additional substrates and roles in epithelial differentiation, barrier function and mucociliary clearance have been described.

Clinical significance: Altered PRSS8 expression or activity has been reported in several diseases. Reduced prostasin expression has been observed in some epithelial cancers and is often linked with tumor progression and promoter methylation; experimental evidence also implicates prostasin in airway and kidney disease models through effects on ENaC and epithelial integrity. However, clinical utility as a biomarker or therapeutic target remains under investigation.

Structure and regulation: PRSS8 encodes a serine protease of the trypsin-like family with the canonical catalytic triad (His-Asp-Ser). The mature enzyme is active extracellularly after propeptide removal and is regulated by endogenous inhibitors and by proteolytic activation by matriptase.