PEPT2 is a mammalian proton driven transporter for di- and tripeptides that shows widespread expression within the organism. Highest expression is found in the kidney where it is supposed to contribute to amino acid homeostasis by reabsorption of filtered peptides. Yet, a mouse model that is deficient in PEPT2 failed to show an obvious phenotype. To elucidate to which extent this lack of a prominent phenotype in Pept2-/- mice is caused by biological redundancy, a comprehensive analysis of mRNA, protein and metabolite levels in kidney tissue samples of transporter-deficient and control animals was performed in combination with the assessment of urinary amino acids and dipeptides. 20k cDNA microarray analysis identified 147 transcripts with significantly altered expression in transporter- deficient animals. Proteome analysis by 2D-PAGE detected 37 proteins with altered levels in Pept2-/- mice of which 17 could be identified by MALDI-TOF-MS. Metabolites determined by GC- TOF-MS revealed prominent changes in levels of a variety of amino acids and derivatives. Urinary loss of cys-gly together with lower concentrations of cysteine, glycine and oxoproline in kidney tissue and altered expression of mRNA and proteins involved in metabolism of GSH suggests that PEPT2 might be a system for reabsorption of substrates for GSH resynthesis.