ATP-binding cassette transporter subfamily D member 1 (ABCD1)

ATP-binding cassette transporter subfamily D member 1 (ABCD1) is a peroxisomal membrane protein that facilitates the transport of very long-chain fatty acids (VLCFAs) from the cytosol into the peroxisome for degradation via beta-oxidation [UniProt: P33897]. This protein is essential for maintaining lipid homeostasis; its deficiency leads to the accumulation of VLCFAs in various tissues, particularly the central nervous system and adrenal glands [NCBI Gene: 215]. Mutations in the ABCD1 gene are the primary cause of X-linked adrenoleukodystrophy (X-ALD), a progressive and often fatal neurodegenerative disorder characterized by demyelination and adrenal insufficiency [PubMed: 28258356]. In modern therapeutics, ABCD1 is a major target for gene therapy, with elivaldogene autotemcel being the first approved treatment to deliver a functional cDNA copy of the gene into patient stem cells [FDA, 2022]. Ongoing pharmacological research also explores the upregulation of the redundant transporter ABCD2 and the use of PPAR-gamma agonists to mitigate the metabolic and inflammatory hallmarks of the disease [PubMed: 30121175].

Other names

Adrenoleukodystrophy proteinALDPABC42AMN

Gene replacement therapy provides a functional copy of the ABCD1 gene to restore protein activity; pharmacological induction of the homologous ABCD2 transporter compensates for ABCD1 deficiency; PPAR-gamma agonism reduces VLCFA levels and neuroinflammation.