MRPL35 (mitochondrial ribosomal protein L35) is a structural component of the mitochondrial large ribosomal subunit that plays essential roles in mitochondrial protein synthesis and cellular homeostasis 1. Beyond its canonical function in mitochondrial translation, MRPL35 exhibits significant extra-mitochondrial functions and demonstrates oncogenic properties across multiple cancer types 2. The protein is consistently overexpressed in colorectal cancer, non-small cell lung cancer (NSCLC), and hepatocellular carcinoma, where high expression correlates with poor patient survival 234. Mechanistically, MRPL35 promotes cancer cell proliferation, invasion, and metabolic reprogramming by regulating reactive oxygen species (ROS) production and activating key signaling pathways including p53, cell cycle regulation, and glutamine metabolism 25. The protein is stabilized through USP39-mediated deubiquitination and functions by upregulating SLC7A5 expression to enhance glutamine metabolism in NSCLC 5. Conversely, MRPL35 downregulation leads to increased ROS production, DNA damage, cell cycle arrest, and apoptosis 2. In liver disease, MRPL35 exhibits protective effects against neonatal parenteral nutrition-associated cholestasis by modulating the ROS/JNK/NF-κB pathway and reducing inflammatory responses 6. These findings position MRPL35 as a promising therapeutic target for cancer treatment and liver disease management.