The epithelial sodium channel (ENaC) is the rate limiting step for sodium absorption in a number of epithelial tissues including the aldosterone sensitive nephron. The appropriate regulation of renal ENaC activity is important for the maintenance of body sodium balance and blood pressure control (2). This is evidenced by gain-of-function mutations of ENaC which cause a severe form of salt-sensitive arterial hypertension known as Liddle's syndrome. Proteolytic processing of ENaC along its biosynthetic pathway is thought to contribute to its activation under physiological and pathophysiological conditions (4). Several protease cleavage sites have been identified in the extracellular loop of the a - and g -subunit of ENaC, and cleavage of the g -subunit plays a critical role for the proteolytic activation of so called near-silent channels (1). Most of our knowledge about ENaC activation by extracellular proteases stems from studies in model system like Xenopus laevis oocytes and cultured cells. However, functional evidence is emerging that ENaC activation by extracellular proteases can occur in native renal tissue (3). Inappropriate ENaC activation by endogenous proteases, e.g. plasmin, may be involved in sodium retention in nephrotic syndrome (5). Proteolytic activation of ENaC may also contribute to the pathophysiology of arterial hypertension in the context of renal disease associated with the release of local proteases. However, the (patho- ) physiologically relevant proteases remain to be identified.

1. Diakov A, Bera K, Mokrushina M, Krueger B, Korbmacher C. 2008. J Physiol 586, 4587–4608

2. Loffing J, Korbmacher C. 2009. Pflügers Arch 458, 111–135

3. Nesterov V, Dahlmann A, Bertog M, Korbmacher C. 2008. Am J Physiol 295, F1052–1062 4. Rossier BC, Stutts MJ 2009. Ann Rev Physiol 71, 361–379

5. Svenningsen P et al. 2008. J Am Soc Nephrol 20, 299–310