Together, these findings suggest that SLC6A14 activity plays a role in the modification of the initial stages of airway infection by altering the level of l-arginine in the ASL, which in turn affects the attachment of <i>P. aeruginosa</i><b>IMPORTANCE</b> CF patients with shared <i>CFTR</i> gene mutations show significant variability in their clinical presentation of infectious lung disease. Here, SLC6A14 is linked to cystic fibrosis.