MRPS12 (mitochondrial ribosomal protein S12) is a structural component of the 28S mitochondrial small ribosomal subunit that regulates mitochondrial translation fidelity 1. As part of the mitochondrial ribosome, MRPS12 controls decoding accuracy and susceptibility to aminoglycoside antibiotics 1. Its expression is transcriptionally regulated through a bidirectional promoter shared with mitochondrial seryl-tRNA ligase (Sarsm), where NF-Y transcription factors act combinatorially on CCAAT boxes to maintain directional selectivity 2. Clinically, MRPS12 demonstrates disease relevance across multiple conditions. In ovarian cancer, MRPS12 is significantly upregulated and associated with poor overall survival in advanced-stage patients with TP53 mutations, functioning as a potential oncogene through enrichment of cell cycle and PI3K/AKT/mTOR signaling pathways 1. Conversely, MRPS12 is downregulated in ischemic stroke, with decreased expression correlating to disease severity 3. In Alzheimer's disease models, the MRPS12 3'UTR localization sequence facilitates mitochondrial trafficking of therapeutic lncMtDloop, improving mitochondrial function and ameliorating AD pathology 4. Metabolic stress studies reveal that MRPS12 mutations affecting translational accuracy produce tissue-specific outcomes: error-prone variants protect cardiac tissue but increase hepatic lipid accumulation, while hyper-accurate variants protect liver but cause cardiomyopathy and reduced lifespan 5.