ACBD5 (acyl-CoA binding domain containing 5) is a peroxisomal membrane protein that serves as a critical tethering factor for peroxisome-endoplasmic reticulum (ER) membrane contact sites and facilitates inter-organellar communication. ACBD5 interacts with ER-resident VAMP-associated proteins (VAPA and VAPB) to form the primary tether connecting peroxisomes to the ER 1. This tethering function is essential for peroxisome maintenance, growth, and lipid homeostasis, including the synthesis of plasmalogen phospholipids and maintenance of cellular cholesterol levels 1. Additionally, ACBD5 forms contacts with mitochondria through interaction with PTPIP51, facilitating ROS transfer from mitochondria to peroxisomes during oxidative stress 2. While ACBD5 acts as the primary tether for very long-chain fatty acid recruitment to peroxisomes, it is not absolutely required for efficient peroxisomal Ξ²-oxidation 3. Loss-of-function mutations in ACBD5 cause a rare peroxisomal disorder characterized by retinal dystrophy with leukodystrophy, presenting with rod monochromatism, progressive leukodystrophy, spasticity, ataxia, and potentially additional features including ovarian insufficiency 45. This disorder demonstrates the critical role of peroxisome-ER contacts in human health.