This article is available online at http://www.jlr.orgPeroxisomes play essential roles in the metabolism of both dietary and endogenously synthesized lipids ( 1, 2 ). The synthesis of the etherphospholipids (platelet activating factor and plasmalogens), partial  -oxidation of verylong-chain fatty acids (VLCFAs; C>22), and the ␣ -oxidation of phytanic acid occur within this organelle. A comprehensive integrative map of peroxisomal metabolic pathways can be found at www.peroxisomedb.org ( 3 ). The importance of the organelle is best exemplifi ed by the occur rence of peroxisome biogenesis disorders and singleenzyme defi ciencies that result in severe metabolic diseases that are often lethal in early childhood. X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder characterized by the accumulation of VLCFA in tissues, progressive demyelination, and adrenocortical dysfunction ( 4 ). X-ALD is caused by mutations in ABCD1 (D1), an ATP binding cassette (ABC) half transporter that presumably mediates the transport of very-long-chain acylCoAs into peroxisomes ( 5 ). D1 is the founding member of a quartet of ABC half-transporters that contain peroxisomal targeting sequences and form heterodimers in vitro ( 6 ). However, homodimers appear to be preferred in vivo, and each subfamily member has a unique tissue distribution ( 7,8 ).The closest paralog to D1 is D2, which shares 66% amino acid identity and is expressed in the adrenal, brain, and liver ( 9 ). Expression of a D2 transgene in D1-defi cient mice partially corrected the phenotype in this mouse Abstract The ATP binding cassette transporter, ABCD2 (D2), is a peroxisomal protein whose mRNA has been detect ed in the adrenal, brain, liver, and fat. Although the role of this transporter in neural tissues has been studied, its function in adipose tissue remains unexplored. The level of immunoreactive D2 in epididymal fat is >50-fold of that found in brain or adrenal. D2 is highly enriched in adipocytes and is upregulated during adipogenesis but is not essen tial for adipocyte differentiation or lipid accumulation in day 13.5 mouse embryonic fi broblasts isolated from D2-defi cient (D2 ؊ / ؊ ) mice. Although no differences were appreci ated in differentiation percentage, total lipid accumulation was greater in D2 ؊ / ؊ adipocytes compared with the wild type. These results were consistent with in vivo observa tions in which no signifi cant differences in adiposity or adipocyte diameter between wild-type and D2؊ / ؊ mice were observed. D2