Glucocorticoids can activate a Na⁺-permeable conductance in H441 airway epithelial cells via a mechanism dependent upon phosphoinositide-3-kinase (PI3K) (Brown et al., 2008; Inglis et al., 2009). It is now well established that PI3K controls the activity of serum and glucocorticoid-inducible kinase 1 (SGK1) (Kobayashi and Cohen, 1999), and this regulatory kinase controls over the abundance of epithelial Na⁺ channels in the plasma membrane. The fact that the transient expression of a constitutively active form of SGK1 (SGK1-S422D) mimics the effects of glucocorticoid stimulation by inducing Na⁺ current (I_Na) in hormone-deprived cells therefore suggests that SGK1 may mediate the physiological effect of glucocorticoid stimulation (Brown et al. 2008). However, not all data are consistent with this hypothesis since we have also shown that activating PI3K, either by insulin stimulation or by the transient expression of a membrane-anchored form of the catalytic PI3K-P110α subunit (CD2-P110α, see Reif et al, 1996) does not alter the electrical properties of hormone-deprived cells. Moreover, we have recently shown that the expression of CD2-P110α does increase cellular SGK1 activity (N. McTacvish and SM Wilson, unpublished) suggests strongly that factors other than SGK1 must contribute to the glucocorticoid-dependent control of I_Na in these cells. It is therefore interesting that studies of renal epithelial cells have shown the glucocorticoid-inducible leucine zipper proteins (GILZ1-3) contribute to the control of I_Na by (i) supressing signalling via extracellular signal dependent kinases (ERK1/2) and (ii) by facilitating the effects of SGK1 upon the abundance of ENaC in the plasma membrane (Soundararajan et al., 2009). The present study therefore explored the effects of GILZ1 upon the electrical properties of hormone-deprived H441 cells. The first such studies confirmed that glucocorticoid-deprived H441 cells do not normally display any I_Na and showed that dexamethasone consistently induced ~60 pA cell^-1 of current (Fig 1A). Although this response is dependent upon PI3K (Inglis et al. 2009), increasing cellular PI3K activity by transient expression of CD2-P110α did not reproduce this physiological response to dexamethasone stimulation (Fig 1B). However, transient expression of GILZ1 consistently induced I_Na indicating that this endogenous protein can fully reproduce the electrophysiological consequences of glucocorticoid stimulation. These data therefore suggest that GILZ1 may contribute to the hormonal control of Na<up>+ transport in human airway epithelia.