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These pathologic features in severe asthma indicate a loss of control of proliferation, cell size, differentiation, and migration. MTOR is a highly conserved pathway that regulates protein synthesis, cell size, and proliferation. We hypothesized that the balance between MTOR and autophagy regulates mucous cell metaplasia. Airways from individuals with severe asthma showed increased MTOR signaling by RPS6 phosphorylation, which was reproduced using an IL-13\u2013activated model of primary human airway epithelial cells (hAEC). MTOR inhibition by rapamycin led to a decrease of IL-13\u2013mediated cell hypertrophy, hyperplasia, and MUC5AC mucous metaplasia. BrdU labeling during IL-13\u2013induced mucous metaplasia confirmed that MTOR was associated with increased basal-to-apical hAEC migration. MTOR activation by genetic deletion of Tsc2 in cultured mouse AECs increased IL-13\u2013mediated hyperplasia, hypertrophy, and mucous metaplasia. 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