These results suggest a mechanism explaining the pathogenesis of autoimmune PAP (Fig. 4): reduced GM-CSF-PU.1-PPARγ axis signaling in alveolar macrophages → reduced ABCG1/ABCA1 expression → reduced cholesterol clearance → secondarily reduced surfactant uptake and clearance (not impaired surfactant phospholipid catabolism) → surfactant accumulation in pulmonary alveoli → clinical manifestations. The gene discussed is SPI1; the disease is autoimmune pulmonary alveolar proteinosis.