MPV17L2 is an integral mitochondrial inner membrane protein essential for mitochondrial ribosome biogenesis and function. MPV17L2 is required for assembly and stability of the mitochondrial ribosome and acts as a positive regulator of mitochondrial protein synthesis 1. Mechanistically, MPV17L2 co-sediments with the large ribosomal subunit and facilitates union of mitochondrial ribosomal subunits to form the translationally competent monosome 1. Depletion of MPV17L2 markedly decreases both ribosomal subunits and impairs mitochondrial protein synthesis, while also inducing mitochondrial DNA aggregation 1. Therapeutically, reducing MPV17L2 expression via miR-34a-5p targeting decreases respiratory chain Complex I activity and ATP production, reducing mitochondrial respiration capacity and increasing oxidative stress in cancer cells 2. Genetic studies identify MPV17L2 as a disease-associated locus near MS-susceptibility SNPs 3 and as a prognostic gene in cigarette-toxicant-induced osteoporosis through mitochondrial regulation pathways 4. Additionally, MPV17L2 expression is downregulated following HDAC11 inhibitor treatment in malignant peripheral nerve sheath tumor cells, contributing to mitochondrial dysfunction 5. These findings establish MPV17L2 as a critical regulator of mitochondrial bioenergetics with potential therapeutic implications in cancer and neurodegenerative disease.