NDUFA6 encodes a 15 kDa accessory subunit of mitochondrial respiratory complex I that is essential for proper complex assembly and function 1. As part of the Q-module, NDUFA6 is required for incorporating other Q-module subunits including NDUFAB1, NDUFA7, and NDUFA12 into the complex, though it does not directly participate in catalysis 1. The protein functions in electron transfer from NADH to ubiquinone and contributes to mitochondrial ATP synthesis. Bi-allelic mutations in NDUFA6 cause early-onset isolated mitochondrial complex I deficiency, presenting with neurological symptoms and elevated lactate levels 1. Beyond its structural role, NDUFA6 serves as a regulatory target - ceramide binding to NDUFA6 can inactivate complex I to reduce oxidative stress in liver ischemia/reperfusion injury 2. The gene also has broader clinical significance, with elevated NDUFA6 expression associated with poor prognosis in acute myeloid leukemia and multiple myeloma 34. Additionally, a missense variant (rs1801311) in NDUFA6 confers schizophrenia risk by affecting transcription factor binding and regulating distant gene expression 5. Gene therapy with NDUFA6 has shown therapeutic potential in treating neurodegeneration in experimental models 6.