FOXA1-mediated CEPT1 deficiency in airway epithelium drives asthma via an ER stress-mitochondrial dysfunction axis

overload, which in turn triggers mitochondrial oxidative stress. Notably, administration of polyenylphosphatidylcholine (PPC) restores ER and mitochondrial homeostasis and reduces apoptosis, cytokine release, and mucus overproduction. FOXA1 is identified as a direct transcriptional activator of CEPT1. In vivo, CEPT1 overexpression alleviates airway inflammation and mucus hypersecretion. Collectively, our study elucidates an axis wherein FOXA1-mediated CEPT1 repression induces ER stress and mitochondrial dysfunction through disrupted calcium handling, driving mucin hypersecretion and airway inflammation-identifying CEPT1 restoration or PPC as potential mechanism-based interventions for asthma.