COQ7 is a mitochondrial diiron hydroxylase that catalyzes the penultimate step of ubiquinone (CoQ10) biosynthesis by hydroxylating 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone at the C6 position 1. The enzyme uses a substrate-mediated reduction mechanism whereby NADH shuttles electrons to the substrate, which then transfers electrons to the diiron centers, enabling oxygen activation for hydroxylation 1. COQ7 adopts a ferritin-like fold with a hydrophobic channel, and functions within a multimeric COQ7:COQ9 complex that accesses lipophilic precursors within the mitochondrial membrane 2. Beyond its catalytic role, COQ7 stabilizes other COQ polypeptides and regulates mitochondrial stress responses through nuclear gene expression independent of ubiquinone biosynthesis 3. COQ7 mutations cause primary CoQ10 deficiency, presenting as neonatal-onset neuromuscular, cardiorespiratory, and renal disease, or late-onset progressive neuropathy with developmental delay 4. Homozygous COQ7 variants have been associated with distal hereditary motor neuropathy and hereditary spastic paraplegia 56. Mechanistically, COQ7 deficiency impairs mitochondrial oxidative phosphorylation, forcing cells toward glycolytic metabolism 5. CoQ10 supplementation or precursor 2,4-dihydroxybenzoic acid can restore function in some patient cells, offering therapeutic potential 54.