TFB1M (transcription factor B1, mitochondrial) is a mitochondrial methyltransferase with dual roles in ribosomal function and transcriptional regulation. As a methyltransferase, TFB1M catalyzes dimethylation of adjacent adenosine residues (A1583 and A1584) in the 12S rRNA loop, a modification essential for small mitochondrial ribosomal subunit assembly and protein translation 1. Beyond its methyltransferase activity, TFB1M functions as a transcription factor required for basal mitochondrial DNA transcription through interactions with POLRMT and TFAM 2. TFB1M dysfunction is implicated in multiple diseases. In type 2 diabetes, common variants in TFB1M (rs950994) and genetic loss-of-function impair insulin secretion by reducing mitochondrial ATP production and oxidative phosphorylation capacity in pancreatic β-cells 31. TFB1M upregulation promotes hepatocellular carcinoma progression by driving a metabolic switch from oxidative phosphorylation to glycolysis, enhancing cell cycle progression and epithelial-mesenchymal transition 4. Genetic variants in TFB1M are associated with kidney disease severity and estimated glomerular filtration rate in both diabetes and non-diabetes populations 5. TFB1M represents a critical node integrating mitochondrial biogenesis with metabolic homeostasis, serving as both a biomarker and potential therapeutic target in metabolic and neoplastic diseases.