MRPL12 (mitochondrial ribosomal protein L12) is a dual-function mitochondrial protein with roles in both translation and transcription regulation. As a component of the mitochondrial large ribosomal subunit, MRPL12 participates in mitochondrial translation 1. When not associated with ribosomes, MRPL12 exists as a free protein that directly binds to mitochondrial RNA polymerase (POLRMT) and activates mitochondrial transcription 2, while also maintaining POLRMT stability 3. This dual functionality coordinates transcription with translation during mitochondrial gene expression. MRPL12 is emerging as a critical regulator of metabolic reprogramming in cancer pathogenesis. In lung adenocarcinoma and hepatocellular carcinoma, elevated MRPL12 expression drives malignant progression by upregulating oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis 45. Notably, MRPL12 Y60 phosphorylation enhances its binding to POLRMT and promotes tumorigenesis, while dephosphorylation by UBASH3B inhibits these oncogenic functions 4. Conversely, in clear cell renal cell carcinoma, MRPL12 is downregulated and functions as a tumor suppressor; K163 acetylation enhances MRPL12-POLRMT binding to promote OXPHOS and suppress glycolysis, inhibiting cancer progression 67. Beyond cancer, MRPL12 dysfunction associates with premature ovarian insufficiency through mitochondrial-immune axis dysregulation 8, and mutations cause combined oxidative phosphorylation deficiency 45. These findings establish MRPL12 as a context-dependent metabolic regulator with potential therapeutic applications.