Allergic asthma is a chronic inflammatory disorder that affects approximately 20% of the population worldwide. Microarray analyses of nasal epithelial cells from acute asthmatic patients detected a 50% decrease in expression of Stard7, an intracellular phosphatidylcholine (PC) transport protein. To determine if loss of Stard7 expression promotes allergic responses, mice were generated in which one allele of the Stard7 locus was globally disrupted (Stard7+/− mice). Ovalbumin (OVA) sensitization and challenge of Stard7+/− mice resulted in a significant increase in pulmonary inflammation, mucous cell metaplasia, airway hyperreactivity (AHR), and OVA-specific IgE compared to OVA sensitized/challenged WT mice. This exacerbation was largely Th2-mediated with a significant increase in CD4+IL-13+ T cells and IL-4, IL-5 and IL-13 cytokines. The loss of Stard7 was also associated with increased lung epithelial permeability and activation of proinflammatory DCs in sensitized and/or challenged Stard7+/− mice. Notably, OVA-pulsed DCs from Stard7+/− mice were sufficient to confer an exaggerated allergic response in OVA-challenged WT mice, although AHR was greater in Stard7+/− recipients compared to WT recipients. Enhanced allergic responses in the lung were accompanied by age-dependent development of spontaneous atopic dermatitis. Overall, these data suggest that Stard7 is an important component of a novel protective pathway in tissues exposed to the extracellular environment.