ABCD3 is an ATP-binding cassette transporter localized to the peroxisomal membrane that catalyzes the transport of long-chain fatty acid-CoA, branched-chain fatty acids-CoA, dicarboxylic acids-CoA, and bile acid intermediates from the cytosol into the peroxisomal lumen for beta-oxidation. The protein possesses both fatty acyl-CoA thioesterase and ATPase activities, with substrate binding inducing conformational changes that activate its ATPase function 1. ABCD3 plays a central role in regulating very long-chain fatty acid catabolism and energy metabolism through peroxisomal fatty acid degradation and bile acid biosynthesis. Pathogenic variants in ABCD3 cause multiple disease states. Mutations are associated with congenital bile acid synthesis defect 5 and Zellweger syndrome variants 1. Recent evidence reveals that CCG repeat expansions in ABCD3, detected in 35 affected individuals across eight families of European ancestry, cause oculopharyngodistal myopathy, characterized by ptosis, dysphagia, distal weakness, rimmed vacuoles, and intranuclear inclusions in muscle 2. The repeat expansions appear to upregulate ABCD3 transcript levels, suggesting that pathogenic excess transcript expression contributes to progressive skeletal muscle degeneration 2. In clear cell renal cell carcinoma, ABCD3 expression is significantly downregulated across all tumor stages, and reduced expression independently predicts poorer overall survival 3, suggesting a tumor-suppressive role in this context.