Acyl-CoA binding domain-containing protein 5 (ACBD5)

Acyl-CoA binding domain-containing protein 5 (ACBD5) is a peroxisomal tail-anchored membrane protein belonging to the acyl-CoA binding protein family, with its acyl-CoA binding domain (ACBD) exposed to the cytosol[1][3]. ACBD5 binds preferentially to very-long-chain fatty acyl-CoAs (VLC-CoAs) and facilitates their uptake into peroxisomes for β-oxidation, thereby playing a key role in cellular lipid homeostasis, especially the degradation of VLCFAs[1][3]. It also acts as a tether connecting peroxisomes to the endoplasmic reticulum (ER) through direct binding to ER-resident VAP proteins, supporting lipid exchange and peroxisomal membrane expansion[3]. Dysfunction or loss of ACBD5 leads to defects in peroxisomal VLCFA metabolism manifesting as disorders including syndromic retinal dystrophy, leukodystrophy, and sometimes neurological or developmental conditions[1][3][4]. Gene fusions involving ACBD5 have been implicated in oncogenic events such as papillary thyroid cancer[3]. There are currently no known drugs directly targeting ACBD5, and the physiological requirement for its function suggests that loss or inhibition could lead to potentially serious metabolic and neurological consequences[1][3][4].

Other names

KIAA1996DKFZp434A2417RDLKDendozepine-related proteinmembrane-associated diazepam binding inhibitor

no known mechanism for drug action directly targeting ACBD5 reported; biological role in facilitating peroxisomal import/oxidation of VLCFAs[1][3]