COQ3 encodes an O-methyltransferase essential for coenzyme Q (ubiquinone) biosynthesis, catalyzing two non-consecutive methylation steps in the pathway 1. The enzyme first methylates 3,4-dihydroxy-5-polyprenylbenzoic acid to form 4-hydroxy-3-methoxy-5-polyprenylbenzoic acid, and also performs the final step by converting 3-demethylubiquinone to ubiquinone 1. COQ3 is ubiquitously expressed across tissues, with highest levels in testis, heart, and skeletal muscle 2. The protein functions as a membrane-binding enzyme with specific affinity for cardiolipin-enriched mitochondrial membranes, facilitated by a unique structural insertion required for membrane association 3. COQ3 exists in multiple protein complexes within mitochondria and plays a critical role in maintaining coenzyme Q stability 4. Mutations in COQ3 are associated with primary coenzyme Q deficiency syndrome, a mitochondrial disorder with diverse clinical manifestations 5. Knockdown studies demonstrate that COQ3 depletion significantly reduces coenzyme Q levels and can cause developmental lethality, indicating its essential role in cellular bioenergetics 6. The protein's critical function in maintaining mitochondrial respiratory chain activity makes it a potential therapeutic target for coenzyme Q deficiency disorders 4.