RPLP2 is a ribosomal lateral stalk protein that plays a specialized role in translational elongation beyond general protein synthesis. As a component of the ribosomal P-stalk, RPLP2 anchors to the 60S large ribosomal subunit through interaction with RPLP0 1. Its primary function involves relieving ribosome pausing during translation, particularly for mRNAs encoding multi-pass transmembrane proteins 2 and viral proteins with atypical structural features 3. Mechanistically, RPLP2 regulates selective rather than global translation. RPLP2 depletion specifically impairs translation of non-canonical mRNAs, such as poxvirus late transcripts with poly(A) leaders and coronavirus transcripts, while having minimal impact on global protein synthesis 14. RPLP2 expression decreases in senescent cells, correlating with altered translational efficiency for senescence-related genes through ribosome heterogeneity 5. Clinically, RPLP2 demonstrates oncogenic properties. High RPLP2 expression in lung adenocarcinoma correlates with poor prognosis, worse overall survival, and altered immune infiltration 6. In hepatocellular carcinoma, RPLP2 promotes cellular migration and invasion; conversely, METTL14-mediated m6A methylation of RPLP2 reduces its stability and suppresses malignant behaviors 7. These findings suggest RPLP2 is a potential therapeutic target for cancer and viral infections.