Complexome profiling revealed TMEM126B to be a component of the mitochondrial complex I assembly (MCIA) complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1, thus establishing TMEM126B (MIM: 615533) as a candidate gene for complex I deficiency.10, 11 With access to subjects harboring putative TMEM126B defects, we provide functional evidence to support the pathogenicity of these TMEM126B variants, unequivocally establishing this gene as a cause of complex I deficiency in association with either a severe multisystem presentation in infancy or pure myopathy in later child- or adulthood. The gene discussed is TMEM126B; the disease is hyperinsulinemic hypoglycemia, familial, 4.