As SCNN1B is a lowly expressed gene, interference with SCNN1B gene regulation by naturally occurring polymorphisms such as rs2303153 is likely to affect ENaC function through perturbation of SCNN1B expression levels and/or transcript stability, which explains the role of SCNN1B as a modifier of cystic fibrosis disease severity. The gene discussed is SCNN1B; the disease is cystic fibrosis.