NDUFS4 is a non-enzymatic 18 kDa nuclear-encoded subunit that, according to the most recent cI assembly model, appears to be incorporated at a relatively late stage.2 Mutations in the NDUFS4 gene are associated with Leigh syndrome (LS), a fatal progressive neurodegenerative condition of childhood characterized by symmetrical necrotizing lesions of the basal ganglia, thalamus, brainstem and cerebellum. Here, NDUFS4 is linked to Leigh syndrome.