Prostasin (Serine protease 8) (PRSS8)

Prostasin, encoded by the PRSS8 gene, is a glycosylphosphatidylinositol (GPI)-anchored serine protease primarily expressed in the apical membranes of epithelial cells in the kidney, lung, and skin [UniProt P65758]. Its most well-characterized biological function is the proteolytic activation of the epithelial sodium channel (ENaC), a critical regulator of sodium reabsorption and fluid homeostasis [PubMed 11035010]. By cleaving the gamma subunit of ENaC, prostasin increases the open probability of the channel, thereby promoting sodium uptake. This mechanism makes PRSS8 mRNA a significant therapeutic target for conditions characterized by ENaC overactivity, such as hypertension and cystic fibrosis [PubMed 18434543, PubMed 25341145]. In cystic fibrosis, reducing prostasin levels via antisense oligonucleotides or siRNA aims to limit sodium hyperabsorption in the airways, potentially improving mucus clearance. Beyond its role in ion transport, prostasin is essential for the formation of the epidermal permeability barrier, and its downregulation is frequently observed in various epithelial cancers, suggesting a role as a tumor suppressor [PubMed 15621726].

Other names

Serine protease 8Channel-activating protease 1CAP1PRSS8 mRNA

Reduction of prostasin protein levels via mRNA degradation (antisense or siRNA) or direct enzymatic inhibition, resulting in decreased proteolytic cleavage and activation of the epithelial sodium channel (ENaC).