SCNN1D encodes the delta subunit (δ-ENaC) of the epithelial sodium channel, a fourth subunit unique to humans and primates that differs from the classical α, β, and γ subunits found in mice 1. The primary function of δ-ENaC is to regulate sodium transport and fluid homeostasis across epithelial membranes, particularly in respiratory tissues 2. Functionally, δ-ENaC operates as an amiloride-inhibitable sodium channel that can be distinguished from α-ENaC by its sensitivity to α-13 inhibitory peptide 2. The channel facilitates fluid absorption in lung tissues, as demonstrated by transgenic expression studies showing enhanced fluid clearance in fetal lung explants 3. δ-ENaC also regulates alveologenesis by facilitating proliferation of alveolar type 2 epithelial cells 2. Disease relevance includes associations with cystic fibrosis severity, where rare variants in SCNN1D may confer a milder pulmonary phenotype through hypomorphic channel activity 4. Additionally, SCNN1D variants have been linked to coronary artery disease risk through super enhancer mechanisms 5 and identified as novel genetic determinants of telomere length 6. The channel is also expressed in cardiac fibroblasts, suggesting broader physiological roles beyond respiratory function 7.