CSF2RA encodes the alpha subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, a low-affinity receptor that transduces signals promoting proliferation, differentiation, and functional activation of hematopoietic cells through JAK-STAT signaling pathways. Located in the pseudoautosomal region of the X and Y chrX|Y, CSF2RA is expressed on the cell surface and binds GM-CSF as part of a heterodimeric receptor complex. Loss-of-function mutations in CSF2RA cause hereditary pulmonary alveolar proteinosis (PAP), characterized by impaired GM-CSF-dependent surfactant clearance by alveolar macrophages, leading to progressive dyspnea and hypoxemic respiratory failure 1. Genetic variants including novel hemizygous deletions have been documented in pediatric cases 2. Beyond PAP, CSF2RA deletions in the pseudoautosomal region contribute to poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia when co-occurring with other deletions 3. In immune contexts, CSF2RA expression on pro-inflammatory monocytes has been implicated in immune checkpoint inhibitor-related pneumonitis, where GM-CSF-producing pathogenic T-helper 17.1 cells establish a feedforward loop with CSF2RA-expressing myeloid cells 4. Recent evidence suggests CSF2RA promotes gastric cancer progression through JAK2/STAT3 pathway activation 5. Clinically, whole-lung lavage remains the cornerstone therapy for PAP 2, while lentiviral vector-mediated gene transfer approaches show promise for restoring GM-CSF receptor function 6. Approved therapies targeting GM-CSF signaling, including sargramostim and mavrilimumab, may benefit patients with CSF2RA-related disorders.