RPF2 (ribosome production factor 2 homolog) is a nucleolar protein essential for ribosomal large subunit (LSU) biogenesis. Its primary function involves chaperoning 5S rRNA assembly into the 5S ribonucleoprotein particle (RNP) 1. RPF2 forms a specialized complex with Rrs1 that contains a 5S RNA-binding module and contacts ribosomal proteins Rpl5 and Rpl11, establishing interactions that guide incorporation of the 5S RNP into preribosomes prior to rotation into the mature LSU central protuberance 1. The protein localizes primarily to the nucleolus 2. Beyond ribosome assembly, RPF2 has emerged as an oncogenic factor across multiple cancers. In hepatocellular carcinoma (HCC), high nuclear RPF2 expression correlates with poor prognosis, vascular invasion, and advanced tumor characteristics; RPF2 overexpression promotes cell proliferation, migration, and invasion 2. Similarly, in colorectal cancer (CRC), RPF2 drives metastasis through epithelial-mesenchymal transition (EMT) via the AKT/GSK-3β signaling pathway, with CARM1 as a critical mediator 3. In collecting duct carcinoma, elevated RPF2 associates with malignant phenotypes and enhanced ribosome biogenesis; targeting RPF2 suppresses ribosome biogenesis and disrupts MDM2-p53 interaction 4. RPF2 represents a promising therapeutic target and biomarker for cancer prognosis and treatment.