Biochemical Aspects of X‐Linked Adrenoleukodystrophy

Abstract

X‐linked adrenoleukodystrophy (X‐ALD) is the most common peroxisomal disorder. The disease is characterized by the accumulation of very long‐chain fatty acids (VLCFA; >C22) in plasma and tissues. X‐ALD is caused by mutations in the ABCD1 gene encoding ALDP, an adenosine triphosphate (ATP)‐binding‐cassette (ABC) transporter located in the peroxisomal membrane. In this paper, we describe the current knowledge on the function of ALDP, its role in peroxisomal VLCFA beta‐oxidation and the consequences of a defect in ALDP on VLCFA metabolism. Furthermore, we pay special attention to the role of the VLCFA elongation system in VLCFA homeostasis, with elongation of very long‐chain fatty acids like‐1 (ELOVL1) as key player, and its relevance to X‐ALD.