TMEM126A is a mitochondrial inner membrane protein that plays essential roles in mitochondrial complex I assembly and protein quality control. The protein functions as an assembly factor specifically required for the ND4 module of mitochondrial complex I 1. TMEM126A associates with newly synthesized polypeptides and acts as a chaperone that cooperates with OXA1L for the cotranslational insertion of mitochondrial proteins into the inner membrane 1. The protein localizes to the cristae of the inner mitochondrial membrane, where its mRNAs are enriched near mitochondria for local translation 2. TMEM126A mutations cause autosomal recessive optic atrophy (optic atrophy 7), a hereditary optic neuropathy affecting retinal ganglion cells 34. Loss of TMEM126A results in isolated complex I deficiency and mitochondrial dysfunction 1. Beyond its mitochondrial roles, TMEM126A has been implicated in cancer biology, where its loss promotes breast cancer metastasis through mitochondrial dysfunction-induced oxidative stress and epithelial-to-mesenchymal transition 5. The protein also functions in immune signaling by coupling with CD137L reverse signals in myeloid cells 6.