fig2

Figure 2. Schematic Representation of the Molecular Mechanisms, Biochemical Defects, and Organellar Dysfunctions Driving the Pathogenesis of ALD (Created in https://BioRender.com). In ALD, ABCD1 gene mutation results in impaired ALD protein (ALDP), which plays a critical role in very long-chain fatty acid (VLCFA) metabolism; therefore, a defect in ALDP leads to VLCFA accumulation. Excessive VLCFAs trigger endoplasmic reticulum (ER) stress, ultimately leading to lipoapoptosis. Additionally, VLCFAs induce the production of reactive oxygen species (ROS) and oxidative stress, which in turn cause mitochondrial dysfunction. This creates a vicious cycle that exacerbates disease progression. Taken together, these processes contribute to the clinical manifestations in patients with ALD, including neuroinflammation, demyelination, adrenal insufficiency, and axonal degeneration. ALD: Adrenoleukodystrophy.