GEMIN5 exerts key biological functions regulating pre-mRNAs intron removal to generate mature mRNAs. A series of patients were reported harboring mutations in GEMIN5. No treatments are currently available for this disease. We treated two of these patients with oral Coenzyme Q10(CoQ10), which resulted in neurological improvements, although MRI abnormalities remained. Whole Exome Sequencing demonstrated compound heterozygosity at the GEMIN5 gene in both cases: Case one: p.Lys742* and p.Arg1016Cys; Case two: p.Arg1016Cys and p.Ser411Hisfs*6. Functional studies in fibroblasts revealed a decrease in CoQ10biosynthesis compared to controls. Supplementation with exogenous CoQ10restored it to control intracellular CoQ10levels. Mitochondrial function was compromised, as indicated by the decrease in oxygen consumption, restored by CoQ10supplementation. Transcriptomic analysis of GEMIN5 patients compared with controls showed general repression of genes involved in CoQ10biosynthesis. In the rigor mortisdefective flies, CoQ10levels were decreased, and CoQ10supplementation led to an improvement in the adult climbing assay performance, a reduction in the number of motionless flies, and partial restoration of survival. Overall, we report the association between GEMIN5 dysfunction and CoQ10deficiency for the first time. This association opens the possibility of oral CoQ10therapy, which is safe and has no observed side effects after long-term therapy.