COQ2 encodes a polyprenyltransferase that catalyzes the second step in coenzyme Q10 (CoQ10) biosynthesis by mediating the prenylation of para-hydroxybenzoate with decaprenyl diphosphate 1. This enzyme is essential for CoQ10 production, which serves as a vital electron transporter in the mitochondrial respiratory chain and plays roles in cellular energy metabolism. Pathogenic variants in COQ2 cause primary CoQ10 deficiency, a rare mitochondrial disorder presenting with steroid-resistant nephrotic syndrome, often manifesting in infancy with kidney disease occurring at median age 1.0 years 2. Clinical presentations include glomerulopathy, encephalopathy, developmental delays, and multiorgan involvement, with 50% of patients progressing to kidney failure by age five 2. Recent studies demonstrate that 4-hydroxybenzoic acid supplementation can effectively treat COQ2-related deficiency by serving as a biosynthetic precursor, showing superior efficacy compared to conventional CoQ10 supplementation in both preclinical models and early human trials 3. Additionally, COQ2 variants, particularly V393A, are associated with increased susceptibility to neurodegenerative diseases including Parkinson's disease and multiple system atrophy, especially in early-onset cases 4. High-dose CoQ10 supplementation remains the primary therapeutic approach, though targeted substrate enhancement with 4-hydroxybenzoic acid shows promise for improved outcomes 53.