NUTF2 (nuclear transport factor 2) is a GDP-binding protein that mediates the nuclear import of RAN-GDP from the cytoplasm, a process essential for cargo receptor-mediated nucleocytoplasmic transport. NUTF2 interacts with GDP-bound RAN in the cytosol, recruits it to nuclear pore complexes via nucleoporin interactions, and promotes its nuclear import. Mechanistically, NUTF2's binding to RAN is required for its inhibition of nuclear expansion and regulation of nuclear pore complex diameter, with elevated NUTF2 levels negatively correlating with nuclear size 1. In disease contexts, NUTF2 expression is significantly elevated in multiple cancer types. Pan-cancer analysis reveals NUTF2 as an independent prognostic factor associated with poor survival outcomes in several tumor types, including head and neck squamous cell carcinoma 234. NUTF2 expression correlates positively with cancer proliferation biomarkers (MKI67, PCNA) and epithelial-mesenchymal transition markers, suggesting roles in cancer proliferation and metastasis. Additionally, NUTF2 shows negative correlation with CD8+ T cell and B cell infiltration, implicating it in immune regulation 43. NUTF2 also serves as a prognostic biomarker in non-small cell lung cancer immunotherapy response, with elevated urine NUTF2 levels associated with shorter progression-free survival 5. Recent evidence indicates EGFR-induced dissociation of NUTF2 assemblies can modulate estrogen receptor activity in breast cancer 6.