The mineralocorticoid hormone aldosterone controls blood pressure by regulating sodium reabsorption across epithelial cells of the Aldosterone sensitive distal nephron. The epithelial sodium channel (ENaC) is activated by aldosterone partially via induction of Sgk1 that prevents ENaC ubiquitylation. We identified early aldosterone-regulated mRNAs in mouse distal nephron by AffymetrixTM Gene Chip analysis. Next to Sgk1 we detected~20 other mRNAs, regulated >=2-fold within 1 hour. The mRNAs of two deubiquitylating enzymes, Usp2-45 and Usp53, and a voltage-gated proton channel (Hv1) were among them. The Hv1 could play an important role in the context of aldosterone induced proton secretion in the collecting duct. We plan to obtain more information about the localization of Usp53 and the Hv1 using immunofluorescence and qRT PCR. Coexpression of Usp2-45 was shown to increase ENaC function in X. laevis oocytes and in mouse cortical collecting duct cells, by using voltage-clamp techniques. The Usp53 in contrast did not affect ENaC function but Usp53t (lacking the catalytic domain) increased the exogenous Na,K-ATPase current in coinjected X. laevis oocytes. The observation, that aldosterone-induced Usps stimulate the function of ENaC and of the Na,K-ATPase supports the hypothesis, that ubiquitylation and deubiquitylation plays a central role in transepithelial sodium transport regulation.