Thus, our data demonstrate that not only robust CD116 expression levels in macrophages can be achieved by targeting the codon-optimized CSF2RA gene into the AAVS1 safe harbor site of PAP patient-derived iPSCs but also receptor downstream signaling and GM-CSF receptor dependent functions such as GM-CSF clearance could be restored. This evidence concerns the gene CSF2RA and pulmonary alveolar proteinosis.