Recently, we further discovered that ISM1 deficiency in mice (Ism1−/−) led to spontaneous low-grade lung inflammation and emphysema at young adult stage (2 months old), accompanied with increased proportion of proinflammatory alveolar macrophages (AMs) that harbor high level of cell surface GRP78 (csGR78) in the AM population. Here, ISM1 is linked to pulmonary emphysema.