{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COQ2 encodes the enzyme para‐hydroxybenzoate‐polyprenyl transferase, a critical catalyst in the biosynthesis of coenzyme Q₁₀ (CoQ₁₀), which serves as a mobile electron and proton carrier in the mitochondrial respiratory chain. Disruption of COQ2 function—whether by missense mutations, frameshift deletions, or other deleterious variants—leads to impaired CoQ₁₀ production and has been directly linked to a heterogeneous spectrum of primary CoQ₁₀ deficiency syndromes. These disorders may present as infantile encephalomyopathy, multisystem disease with renal involvement (including glomerular lesions), myopathy, and features of multiple system atrophy (MSA)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional studies—including yeast complementation assays—have confirmed that mutant forms of COQ2 fail to catalyze the key prenylation step in CoQ₁₀ synthesis, thus establishing a causal connection between COQ2 loss‐of‐function and deficient mitochondrial electron transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical role in mitochondrial bioenergetics, impaired COQ2 activity has emerged as an important genetic risk factor in neurological disorders. Both homozygous and compound heterozygous mutations as well as heterozygous functionally impaired variants of COQ2 have been associated with sporadic and familial cases of multiple system atrophy, underscoring the enzyme’s relevance to neurodegenerative disease via its regulation of CoQ₁₀ levels in affected tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, emerging pharmacogenetic evidence suggests that common genetic variation in COQ2 may influence statin tolerance, possibly by modulating CoQ₁₀ levels in skeletal muscle, although such associations have been observed with milder phenotypes in statin-induced myopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the collected findings indicate that COQ2 plays a central role in CoQ₁₀ biosynthesis. Its proper function is essential for maintaining mitochondrial respiratory chain integrity, and disruptions in COQ2 activity—whether through rare pathogenic mutations or common genetic variants—can lead to a range of multisystem clinical manifestations, from severe metabolic and neuromuscular disorders to altered drug responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Catarina Quinzii, Ali Naini, Leonardo Salviati, et al. 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