COQ6 is a FAD-dependent mitochondrial monooxygenase essential for ubiquinone (coenzyme Q10) biosynthesis 12. The enzyme catalyzes two non-consecutive hydroxylation reactions: C5-ring hydroxylation of 4-hydroxy-3-(all-trans-decaprenyl)benzoic acid and C1-hydroxylation of 2-methoxy-6-(all-trans-decaprenyl)phenol, with electrons supplied indirectly from NADPH via the FDX2/FDXR ferredoxin system 12. Ubiquinone is critical for mitochondrial electron transport chain function and ATP production 3. COQ6 mutations cause primary coenzyme Q10 deficiency with diverse clinical manifestations. The distinctive COQ6-associated phenotype comprises steroid-resistant nephrotic syndrome (SRNS) with sensorineural hearing loss, typically manifesting in infancy 4. SRNS caused by COQ6 mutations shows renal biopsy findings of focal segmental glomerulosclerosis or diffuse mesangial sclerosis, with approximately 50% of patients progressing to kidney failure by age five 45. Additional manifestations include neurological symptoms, growth retardation, and cardiovascular abnormalities 5. CoQ10 supplementation effectively reverses nephrotic-range proteinuria and restores renal function when initiated early 56. Beyond primary CoQ deficiency, reduced COQ6 expression associates with age-related oocyte dysfunction and infertility 3, while COQ6 variants increase pneumococcal disease susceptibility through altered inflammatory-metabolic remodeling 7. A heterozygous COQ6 mutation was identified in familial schwannomatosis, suggesting haploinsufficiency-mediated disease involvement 8.