In vitro studies reported here demonstrate that lentiviral silencing of Abcd1 in human U87 astrocytes and rat B12 oligodendrocytes resulted in reduced β-oxidation and accumulation of VLCFA and, in a novel observation, upregulated ELOVL1 and ELOVL3 to a much greater degree in Abcd1-deficient oligodendrocytes than in Abcd1-deficient U87 astrocytes, suggesting a predominant role for peroxisomal dysfunction in oligodendrocytes contributing to the overall X-ALD neuropathology. This evidence concerns the gene ELOVL3 and X-linked adrenoleukodystrophy.