Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:17577581, PubMed:17540762, PubMed:17267394, PubMed:17142808, PubMed:20190032, PubMed:28034695). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:17142808). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (By similarity). 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) + ATP + H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out) + ADP + H(+) + phosphate a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2. ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2. 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) + phosphate Homooligomer; disulfide-linked. Localized in the limiting membrane of lamellar bodies in lung alveolar type II cells (PubMed:11940594). Trafficks via the Golgi, sorting vesicles (SVs) and late endosome/multivesicular body network directly to the outer membrane of lamellar bodies in AT2 lung epithelial cells or to lysosomes and lysosomal-related organelles (LROs) in other cells where undergoes proteolytic cleveage and oligosaccharide processing from high mannose type to complex type. Oligomers formation takes place in a post-endoplasmic reticulum compartment (By similarity). Highly expressed in the lung and moderately expressed in the kidney, adipose, macrophage, and spleen. Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain. N-glycosylated. Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type. N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation. Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa. Homozygous knockout mice for ABCA3 are die within one hour after birth (PubMed:17577581, PubMed:17540762, PubMed:17267394). Mice develop respiratory failure immediately after birth with clinical signs such as gasping, cyanosis, failure to achieve inflation of the lung as visible through the skin and reduced motor activity and (PubMed:17577581, PubMed:17142808, PubMed:17267394). Conditional knockout mice in which ABCA3 is deleted in alveolar type II cells die shortly after birth from respiratory distress related to surfactant deficiency but approximately 30% of these mice survive after birth and develop emphysema in the absence of significant pulmonary inflammation (PubMed:20190032). Belongs to the ABC transporter superfamily. ABCA family.