ABCA3 is an ATP-dependent phospholipid transporter predominantly expressed in alveolar type II cells that catalyzes the transport of phosphatidylcholine and phosphoglycerol from the cytoplasm into lamellar bodies, critical organelles for pulmonary surfactant synthesis and storage 1. The protein preferentially transports phosphatidylcholine with short acyl chains and also functions as an efflux transporter of free cholesterol and miltefosine, protecting cells from cholesterol toxicity 2. ABCA3 is essential for normal lamellar body biogenesis and surfactant homeostasis, with expression developmentally regulated and peaking before birth 1. Biallelic ABCA3 mutations represent the most frequent genetic cause of congenital surfactant deficiency and childhood interstitial lung disease (chILD), producing disease ranging from neonatal respiratory distress to chr16 diffuse parenchymal lung disease 1. Over 200 mutations have been identified, predominantly unique to families 1. Mutations affecting the first extracellular loop and second nucleotide-binding domain account for much phenotypic diversity through defective glycosylation, trafficking defects, and impaired ATP binding 1. Null mutations (frameshift/nonsense) predict neonatal presentation and poor prognosis, while missense and splice-site mutations show variable age-of-onset and clinical course 3. Recent iPSC-derived models demonstrate that ABCA3-mutant alveolar epithelial cells exhibit diminished surfactant secretion, reduced progenitor potential, and increased pro-inflammatory signaling 4. Currently, no proven therapy exists, though hydroxychloroquine response appears variant-dependent 5.