PRSS8 and nephrotic syndrome: To determine whether prostasin activation or prostasin activity is essential for proteolytic ENaC activation and sodium retention in experimental nephrotic syndrome, we administered doxorubicin to Prss8-wildtype mice and those with point mutations of Prss8 at the activation site (Prss8-R44Q) or the active site (Prss8-S238A).