SURF6 (surfeit 6) is a nucleolar protein with dual roles in ribosomal biogenesis and cell proliferation regulation. Functionally, SURF6 binds both DNA and RNA with preferential RNA binding capacity 1 and serves as a nucleolar constitutive protein involved in ribosomal assembly. Mechanistically, SURF6 participates in early steps of pre-rRNA processing for both small and large ribosomal subunit maturation 2. It forms phase-separated liquid-phase droplets with nucleophosmin (NPM1) through electrostatic interactions, creating dynamic scaffolding networks that facilitate ribosomal biogenesis within the nucleolus 3. SURF6 expression is tightly linked to cell proliferation; it is absent in resting lymphocytes but highly expressed upon activation and in lymphoproliferative disorders, with expression levels correlating with disease aggressiveness 4. SURF6 knockdown alters cell cycle distribution independently of p53 status 2. Disease relevance emerges from multiple contexts: in colorectal cancer, SURF6 is part of a miR3655/SURF6/IRF7/IFNβ regulatory axis where elevated SURF6 suppresses interferon-beta production and promotes bacterial colonization 5, while genetic studies suggest SURF6 inversely associates with endometriosis risk 6. These findings position SURF6 as a multifunctional nucleolar protein integrating ribosomal biogenesis with immune and proliferative signaling.