MRPS15 (mitochondrial ribosomal protein S15) is a mitochondrial ribosomal protein that functions as a structural component of the mitochondrial small ribosomal subunit, essential for mitochondrial translation and oxidative phosphorylation 1. Beyond its canonical mitochondrial role, MRPS15 exhibits moonlighting functions in stressed cells: it localizes to cytosolic ribosomes during endoplasmic reticulum stress, where it acts as an activator of IRES-dependent translation and regulates translation of unfolded protein response mRNAs 2. MRPS15 expression is dysregulated across multiple disease contexts. In hepatocellular carcinoma, MRPS15 is significantly upregulated and serves as both a diagnostic marker and prognostic gene; integration of MRPS15 with ferroptosis-related genes achieved superior HCC prognostic performance 1. In lung adenocarcinoma, MRPS15 overexpression correlates with poor overall survival and contributes to metabolic reprogramming through enhanced mitochondrial translation and OXPHOS 3. In breast cancer, MRPS15 is elevated in epithelial cancer cells and associated with poor clinical outcomes 4. Conversely, MRPS15 is significantly downregulated in non-obstructive azoospermia patients, where it functions as a diagnostic biomarker when combined with other mitochondrial dysfunction-related genes 5. These findings establish MRPS15 as a multifunctional protein with critical roles in metabolic reprogramming and stress response, with emerging clinical significance as a cancer biomarker and diagnostic indicator for male infertility.