GRB2-associated-binding protein 1 (Gab1) belongs to Gab adaptor family (Gabs), which integrates multiple signals in response to the epithelial growth factors. Recent genetic studies identified genetic variants of human Gab1 gene as potential risk factors of asthmatic inflammation. However, Gab1 functions in lungs remain largely unknown. Alveolar type-II cells (AT-IIs) are responsible for surfactant homeostasis, and essentially regulate lung inflammation following various injuries. Here, in vitro knockdown of Gab1 was shown to cause a decrease in surfactant proteins (SPs) in AT-IIs. We further examined in vivo Gab1 functions by generating alveolar epithelium-specific Gab1 knockout mice (Gab1/). In vivo Gab1 deficiency leads to a decrease in SP synthesis and the appearance of disorganized lamellar bodies. Histological examination shows no apparent pathological alterations or inflammation in the lung sections obtained from Gab1/, compared with the controls. However, Gab1/ mice demonstrate inflammatory responses during the LPS-induced acute lung injury. Similarly, in mice challenged with bleomycin (BLM), fibrotic lesions were shown to be aggravated in Gab1/. These observations suggest that the abolishment of Gab1 in AT-IIs impairs SP homeostasis, predisposing mice to lung injuries. Additionally, we observed that the production of surfactants in AT-IIs overexpressing Gab1 mutants, in which Shp2 phosphatase and PI3K kinase binding sites have been mutated (Gab1Shp2, Gab1PI3K), has been considerably attenuated. Together, these findings provide the first evidence of the roles of docking protein Gab1 in lungs, adding to our understanding of acute and interstitial lung diseases caused by the disruption of alveolar SP homeostasis.