MTERF3 (mitochondrial transcription termination factor 3) is a negative regulator of mammalian mitochondrial DNA (mtDNA) transcription that plays critical roles in mitochondrial bioenergetics and cellular homeostasis. MTERF3 binds to mtDNA promoter regions and represses transcription initiation on both mtDNA strands, thereby regulating the expression of oxidative phosphorylation (OXPHOS) complexes and maintaining appropriate levels of mitochondrial transcripts 1. The protein is essential for normal mitochondrial function, maintaining 16S rRNA levels and facilitating mitochondrial ribosome assembly through regulation of 39S ribosomal subunit biogenesis. MTERF3 dysregulation is implicated in multiple disease contexts. In hyperglycemic stress, elevated MTERF3 expression via the NR2F2 pathway suppresses OXPHOS and impairs skin integrity and collagen biosynthesis 2. Loss-of-function MTERF3 mutations cause developmental delay, intermittent hypoglycemia, and metabolic acidosis through impaired mitochondrial respiration and reduced OXPHOS complex assembly 3. In cancer, MTERF3 expression patterns vary by tumor type: overexpression correlates with poor prognosis in hepatocellular carcinoma and lung adenocarcinoma by promoting cell proliferation, while decreased expression associates with poor outcomes in thyroid carcinoma 4, 5, 6. Additionally, MTERF3 contributes to mitochondrial dysfunction in Parkinson's disease models and modulates mitophagy in chr8 obstructive pulmonary disease 7, 8.