ABCB8 is a mitochondrial ATP-binding cassette transporter that functions as the ATP-binding subunit of the mitochondrial ATP-gated potassium channel (mitoK(ATP)), working alongside the pore-forming subunit CCDC51/MITOK to mediate ATP-dependent potassium currents across the mitochondrial inner membrane 1. The channel is inhibited by elevated ATP levels and activated during ATP depletion, regulating potassium uptake into the mitochondrial matrix 1. Beyond ion transport, ABCB8 serves as a critical mitochondrial iron exporter 2. Overexpression of ABCB8 in cardiomyocytes and transgenic mouse hearts decreased mitochondrial iron accumulation and protected against doxorubicin-induced cardiotoxicity 2. In endothelial cells, ABCB8 prevents iron-dependent oxidative stress through a newly identified ABCB8-iron-TGF-β axis; loss of endothelial ABCB8 triggered pro-inflammatory transcriptional reprogramming and exacerbated atherosclerosis and hypertension in apoE knockout mice 3. Clinically, ABCB8 dysregulation associates with multiple pathologies. Doxorubicin-induced cardiomyopathy patients exhibited markedly elevated mitochondrial iron levels 2. ABCB8 variants link to polyautoimmunity through apoptotic regulation pathways 4. In multiple myeloma, the NEAT1/miR-485-5p/ABCB8 axis promotes malignant progression 5, while ABCB8 contributes to multidrug resistance in melanoma 6.