The mechanisms behind the increased susceptibility and aberrant repair of the airway epithelium in chronic inflammatory respiratory diseases remain poorly understood. The drug transporter OCTN2 (gene symbol: SLC22A5) has been associated with asthma [1]. However, its physiological functions in the lung, and more specifically in the epithelium, are currently unknown. This study investigated the impact of insults associated with asthma on OCTN2 expression levels in airway epithelial cells and the potential implications of the transporter in the dysfunctional epithelium observed in the disease. Layers of the human bronchial epithelial cell line Calu-3 cultured on permeable filters at an air-liquid interface for 21 days were used as a physiologically relevant in vitro model of the bronchial epithelium. They were exposed to lipopolysaccharide (LPS), a common pro-inflammatory stimulant, for 48h or to the aeroallergen house dust mite for 8h twice over 48h. In parallel, they were physically damaged in a scrape wound model and allowed to recover for 48h. Changes in OCTN2 gene and protein expression were measured by quantitative polymerase chain reaction (qPCR) or ‘In-cell’ Western, respectively. Subsequently, the alveolar epithelial cell line A549 was used to evaluate the potential roles of OCTN2 in the mechanism of epithelial healing after injury as well as in airway protection against inflammation. OCTN2 was knocked down in the cell line using siRNA. OCTN2 deficient cell layers were either scratched or challenged with LPS for 6h. Cell recovery after wounding was monitored by time lapse microscopy and by the Presto Blue® cell viability assay while the production of reactive oxygen species (ROS) upon LPS stimulation was measured using the dichlorofluorescein diacetate dye. All three epithelial insults caused fold increases in the expression of OCTN2 in Calu-3 layers. In contrast to wild type cells, OCTN2 knocked down A549 layers failed to repair within 48h. In addition, low expression of the transporter resulted in an increase in ROS formation following cell exposure to LPS. OCTN2 expression in airway epithelial cells was shown to be affected by insults associated with asthma. Our data also suggest the transporter participates in the repair of the airway epithelium after injury and might play a role in the control of oxidative stress during airway inflammation, with possible consequences on the pathophysiology of the disease. The underlying mechanisms remain however to be investigated.