Prostasin

Prostasin, also known as protease serine 8 (PRSS8), is a glycosylphosphatidylinositol (GPI)-anchored serine protease expressed on the surface of epithelial cells. It belongs to the trypsin-like family of serine proteases and is produced as an inactive zymogen that requires proteolytic processing to become active. In many epithelial tissues, prostasin is activated through a proteolytic cascade, with matriptase (ST14) acting as a key activator by cleaving the prostasin zymogen.

A major function of prostasin is to regulate transepithelial sodium transport. It cleaves and activates the gamma subunit of the epithelial sodium channel (ENaC), thereby increasing sodium absorption in renal and airway epithelia. This activity links prostasin to broader processes of fluid and electrolyte balance and airway surface liquid homeostasis. Beyond ENaC regulation, prostasin participates in the maintenance of epithelial barrier function and may influence keratinocyte differentiation and epidermal desquamation in the skin. The enzyme is found in extracellular fluids and at the cell surface, where it can act on various substrates within the pericellular environment.

Clinical and research interest in prostasin centers on its role in cancer biology and tissue remodeling. Altered expression of PRSS8 has been observed in several cancers, with potential context-dependent effects on tumor progression, invasion, and prognosis. Because prostasin is part of a protease cascade with matriptase, its activity is influenced by regulatory networks that coordinate proteolysis at epithelial barriers.

Structurally, prostasin contains a catalytic serine protease domain and a propeptide, with the mature enzyme being anchored to the cell surface via a GPI linkage. The protein is encoded by the PRSS8 gene in humans.