ATP-binding cassette subfamily A member 3 (ABCA3) (ABCA3)

ATP-binding cassette subfamily A member 3 (ABCA3) is a member of the ABC transporter family that is highly expressed in the limiting membrane of lamellar bodies within alveolar type II cells (UniProt: P59951). It functions as an ATP-dependent pump that transports phospholipids and cholesterol into these specialized organelles, which is a critical step in the assembly and storage of pulmonary surfactant (PMID: 14742437). Pulmonary surfactant is essential for reducing surface tension at the air-liquid interface of the alveoli, thereby preventing lung collapse during expiration (StatPearls: NBK526024). Mutations in the ABCA3 gene are a major cause of surfactant metabolism dysfunction, leading to severe, often fatal, respiratory distress syndrome in neonates and chronic interstitial lung disease in children and adults (PMID: 31550165). While there are currently no FDA-approved therapies specifically targeting ABCA3, research is focused on repurposing CFTR modulators like Ivacaftor and using chemical chaperones to restore the function of specific ABCA3 variants (PMID: 28103471, 18065684).

Other names

ABC-C transporterXenobiotic-transporting ATPase ABCA3ATP-binding cassette transporter 3LBM180ABC3EST111653

Experimental pharmacological strategies involve the use of chemical chaperones to correct protein misfolding and trafficking defects, or potentiators to increase the transport activity of ABCA3 proteins already present at the lamellar body membrane (PMID: 28103471, 18065684).