Based on the observation that impaired GM-CSF-dependent cholesterol clearance within alveolar macrophages drives reduction of macrophage-mediated surfactant clearance in Csf2rb−/− mice16, a validated animal model of human PAP17, here, we evaluate cholesterol content in human alveolar macrophages and pulmonary surfactant from PAP patients, and test cholesterol homeostasis as a novel target for development of pharmacotherapy of PAP. This evidence concerns the gene CSF2 and pulmonary alveolar proteinosis.