COQ4 encodes a mitochondrial protein essential for coenzyme Q10 (CoQ10) biosynthesis, functioning as a lyase that catalyzes the oxidative decarboxylation of the C1 carbon of CoQ precursors 1. The protein localizes to the mitochondrial inner membrane and acts both as a structural component of the CoQ biosynthetic complex and as an enzyme performing the C1-decarboxylation step during ubiquinone biosynthesis 21. COQ4 deficiency causes primary CoQ10 deficiency with heterogeneous clinical presentations ranging from severe early-onset neurodegeneration to milder adult-onset hereditary spastic paraplegia (HSP) 34. Three distinct phenotypes have been identified: type 1 with neonatal brain anomalies and epileptic encephalopathy, type 2 with stroke-like lesions, and type 3 with stable disease course 3. Recent studies demonstrate that biallelic COQ4 variants can cause adult-onset ataxia-spasticity spectrum disorders, expanding the known phenotypic range beyond severe pediatric presentations 56. Functional studies in patient cells show reduced COQ4 protein levels, decreased CoQ10 concentrations, and elevated metabolic intermediates, confirming the pathogenic nature of identified variants 34. Clinical response to CoQ10 supplementation remains limited, necessitating alternative therapeutic approaches 3.