The epithelial sodium channel (ENaC) mediates the first step in Na + reabsorptionin epithelial cells such as kidney, colon,andairways and mayconsist of four homologous subunits (α, β, γ, δ). Predominantly, the α-subunit is expressed in these epithelia, and it usually forms functional channels with the β- and γ-subunits. The δ-subunit was first found in human brain and kidney, but the expression was also detected in human cell lines of lung, pancreatic, and colonic origin. When co-expressed with b and γ accessory subunits in heterologous systems, the two known isoforms of the δ-ENaC subunit (δ1 and δ2) can build amiloride-sensitive Na+ channels. In the present study we demonstrate the expression and function of the δ-subunit in human nasal epithelium (HNE). We cloned and sequenced the full-length cDNA of the δ-ENaC subunit and were able to show that in nasal tissue at least isoform 1 is expressed. Furthermore, we performed Western blot analyses and compared the cell surface expression of the d-subunit with the classically expressed α-subunit by using immunofluorescence experiments. Thereby, we could show that the quantity of both subunits is almost similar. In addition, we show the functional expression of the δ-ENaC subunit with measurements in modified Ussing chambers, and demonstrate that in HNE a large portion of the Na + transport is mediated by the δ-ENaC subunit. Therefore, we suppose that the d-subunit may possess an important regulatory function and might interact with other ENaC subunits or members of the DEG/ENaC family in the human respiratory epithelium.