ABCD
The ABCD subfamily comprises four human genes, and ABCD1, ABCD2, ABCD3
encode proteins located in the peroxisome. The ABCD proteins are all
half-transporters and, consequently, function as homo- or heterodimers,
and two of these (ABCD1, ABCD2) take part in the regulation of
very-long-chain fatty acid transport (Dean, 2002).
The mammalian peroxisomal ABC transporters are the adrenoleukodystrophy
protein (ALDP/ABCD1), ALDP-related protein (ALDRP/ABCD2), and a 70-kDa
peroxisomal membrane protein (PMP70/ABCD3). X-linked
adrenoleukodystrophy (X-ALD) is associated with variants in ABCD1
(Mosser et al., 1993) . X-ALD is characterized by the accumulation of
very long-chain fatty acids in the peroxisome that is an outcome of
impaired beta-oxidation. Patients with X-ALD display progressive
demyelination of the neurons in the central nervous system, testicular
malfunction, and adrenal insufficiency (Smith et al., 1999). ABCD2 may
be involved in the metabolic transport of VLCFA’s (Morita & Imanaka,
2012). The function of ABCD3 consists of the transportation of
branched-chain acyl-CoA into peroxisomes. ABCD4 resides in the
mitochondria and the lysosomes. In the lysosomes, ABCD4 is involved in
the transport of vitamin B12 from lysosomes into the cytosol. Mutations
in ABCD4 cause an inborn error of vitamin B12 metabolism,
resulting in the lysosomes failing to release cobalamin resulting in
symptoms mimicking cobalamin deficiency (Kawaguchi & Morita, 2016).