ATP-binding cassette sub-family D member 1 (ABCD1) (ABCD1)

ATP-binding cassette sub-family D member 1 (ABCD1) is a critical peroxisomal membrane transporter protein that facilitates the entry of very long-chain fatty acids (VLCFAs), specifically those with 24 or more carbons, into peroxisomes for breakdown via beta-oxidation (UniProt, 2024). Mutations in the ABCD1 gene result in X-linked adrenoleukodystrophy (X-ALD), a condition where VLCFAs accumulate to toxic levels in the plasma and tissues, leading to demyelination of the central nervous system and adrenal insufficiency (NIH, 2023). Therapeutic strategies focus on functional restoration of the ABCD1 protein or its pathway, primarily through ex vivo gene therapy (e.g., elivaldogene autotemcel) which introduces a functional copy of the gene into hematopoietic stem cells (FDA, 2022). Additionally, pharmacological interventions aim to upregulate the homologous transporter ABCD2 to compensate for the loss of ABCD1 or utilize PPAR-gamma agonists to address the downstream metabolic and inflammatory pathology (PubMed, 2021). Clinical management relies on monitoring VLCFA levels and C26:0-lysophosphatidylcholine as key biomarkers for disease progression and treatment response (Mayo Clinic, 2023).

Other names

Adrenoleukodystrophy proteinALDPAMNALD74ABC42ATP-binding cassette transporter

Functional restoration is achieved through gene replacement therapy using lentiviral vectors to deliver a functional ABCD1 gene to hematopoietic stem cells, or through pharmacological induction of the compensatory transporter ABCD2 and activation of PPAR-gamma pathways to mitigate VLCFA-induced toxicity (FDA, 2022; PubMed, 2021).