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Amino acids and small peptides are very efficiently reabsorbed at the level of the kidney proximal tubule by a series of specialized membrane proteins. In a first step, they are taken up into tubular epithelial cells via secondary active transporters localized at the luminal brush border membrane. Most of these amino acids as well as the amino acids generated by the intracellular hydrolysis of the di-/tripeptides are then transported out of the tubular cell across the basolateral membrane into the interstitial space. This second transport step is mediated by another set of transporters that function as facilitated diffusion pathways and obligatory exchangers. Besides reabsorbing amino acids, proximal tubule cells also contribute to body amino acid metabolism, for instance by producing L-arginine, L-tyrosine and L-serine or by metabolizing L-glutamine to produce ammonia for the urinary excretion of protons. Mutations of genes encoding luminal or basolateral amino acids transporters of proximal tubule cells can cause aminoacidurias and lead in some cases, for instance of cystinuria or lysinuric protein intolerance (LPI), to severe diseases.

The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products.