COQ5 is a mitochondrial C-methyltransferase essential for coenzyme Q10 (CoQ10) biosynthesis. The enzyme catalyzes a critical methylation step in the conversion of 2-decaprenyl-6-methoxy-1,4-benzoquinol to 2-decaprenyl-3-methyl-6-methoxy-1,4-benzoquinol during ubiquinone synthesis [UniProt Function]. Knockdown of COQ5 reduces CoQ10 levels, confirming its central role in this pathway 1. CoQ10 functions as an essential electron carrier in the mitochondrial respiratory chain and participates in cellular redox reactions 2. Biallelic COQ5 mutations cause primary coenzyme Q10 deficiency with a characteristic core phenotype encompassing intellectual disability, encephalopathy, cerebellar ataxia with atrophy, speech regression, developmental delay, and short stature 3. Pathogenic variants include splice-site mutations and missense changes that impair mRNA processing; at least one cryptic splicing variant (c.682-7 T > G) has been identified in patients with non-syndromic retinitis pigmentosa, expanding the neurological manifestations beyond classical CoQ10 deficiency presentations 4. Recent evidence suggests mRNA mis-splicing represents a molecular mechanism underlying COQ5-linked pathology 3. CoQ10 supplementation remains the therapeutic approach for primary biosynthetic deficiencies, though clinical efficacy varies by COQ gene affected.