CSF2RA encodes the alpha subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, a low-affinity receptor that functions as a critical component of the GM-CSF signaling complex. 1 The receptor transduces signals through JAK-STAT pathways that result in proliferation, differentiation, and functional activation of hematopoietic cells, particularly myeloid lineages including macrophages and monocytes. 2 CSF2RA is located in the pseudoautosomal region of the X-Y chrX|Y. 3 Clinically, CSF2RA mutations cause hereditary pulmonary alveolar proteinosis (PAP), a rare interstitial lung disease characterized by progressive surfactant accumulation and respiratory failure. 1 4 The mechanism involves impaired GM-CSF-dependent cholesterol clearance in alveolar macrophages, disrupting their capacity to clear excess pulmonary surfactant. 1 Gene therapy approaches using lentiviral vectors expressing functional CSF2RA have demonstrated restoration of GM-CSF receptor signaling in primary cells without adverse effects. 2 Beyond PAP, dysregulated CSF2RA expression appears relevant to other conditions: genetic variants are associated with colorectal cancer risk, 5 and CSF2RA expression on pro-inflammatory monocytes correlates with immune checkpoint inhibitor-related pneumonitis. 6 Whole-lung lavage remains the clinical standard therapy for hereditary PAP. 4