COX20 encodes an essential assembly factor for mitochondrial respiratory chain complex IV (cytochrome c oxidase) that acts as a chaperone during early stages of COX2 subunit maturation 1. The protein stabilizes newly synthesized COX2 and presents it to metallochaperones SCO1 and SCO2, facilitating incorporation of mature COX2 into the assembling complex IV holoenzyme 2. COX20 interacts directly with newly synthesized COX2, and its absence leads to accumulation of incomplete complex IV subassemblies containing COX1 but lacking COX2 2. Loss-of-function mutations in COX20 cause severe complex IV deficiency and reduce mitochondrial respiration, compromising cellular spare respiratory capacity under metabolic stress 3. Clinically, COX20 deficiency presents as an autosomal recessive mitochondrial disorder characterized by sensory neuronopathy, ataxia, hypotonia, dysarthria, and areflexia 43. The phenotypic spectrum includes early-onset developmental delay, dystonia, and visual impairment 4. COX20 is particularly important for proprioceptive sensory neurons, and its dysfunction represents a key mechanism underlying mitochondrial bioenergetic failure in peripheral sensory neuron disease 3. Multiple pathogenic variants have been identified, including missense mutations and splice site variants that eliminate full-length protein production 56.