Consistent with this role, germline bi-allelic ETHE1 mutations cause ethylmalonic encephalopathy[20-23], a genetic disease in which H2S accumulates in critical tissues and can reach concentrations in the brain that inhibit Cytochrome C Oxidase (COX), blocking mitochondrial respiration, increasing lactic acid accumulation, and inducing encephalopathy [22, 24, 25]. The gene discussed is ETHE1; the disease is ethylmalonic encephalopathy.