The renal epithelial sodium channel (ENaC) is critically important for the maintenance of body sodium balance. Regulation of ENaC function is highly complex and may involve aldosterone induced regulatory proteins. Recently N-myc downstream regulated gene 2 (NDRG2) has been identified as an early aldosterone induced gene (Boulkroun et al. 2002, J Biol Chem 277: 31506–15). We hypothesized that NDRG2 may affect ENaC function. To test this hypothesis we performed co-expression experiments in Xenopus laevis oocytes. We used a long (NDRG2-1.7) and a short (NDRG2-3.3) isoform of NDRG2 differing by 14 amino acids in length. The amiloride-sensitive (2 mM) whole-cell current (DI _ami ) was measured in oocytes expressing ENaC alone or co-expressing ENaC and one of the NDRG2 splice variants (n=12–15 oocytes per group for each batch of oocytes). Coexpression of NDRG2 1.7 and ENaC significantly increased DI_ami in 4 out of 10 batches of oocytes with an average increase of 107 ± 13 %. Similarly, NDRG2-3.3 increased DI_ami in 3 out of 5 batches of oocytes with an average increase of 90 ± 33 %. It is presently unclear why the stimulatory effect of NDRG2 was not observed in all batches of oocytes tested. Nevertheless, our results indicate that NDRG2 is a likely candidate to contribute to aldosterone mediated ENaC regulation.