GNL3L is a nucleolar GTP-binding protein that serves dual roles in cell cycle regulation and ribosome biogenesis. Structurally, GNL3L contains a circularly permuted G-motif and a lysine-rich nucleolar localization signal that mediates its importin-β-dependent transport into the nucleolus 1. Functionally, GNL3L stabilizes the telomeric protein TERF1 during mitosis by preventing its ubiquitination and proteasomal degradation, thereby promoting metaphase-to-anaphase transition and enabling cell proliferation 2. Additionally, GNL3L is essential for normal ribosomal pre-rRNA processing and mature rRNA synthesis 3, a role retained from its ancestral invertebrate GNL3 gene 4. Unlike its paralog nucleostemin, which acquired genome-protective functions in vertebrate evolution, GNL3L maintains the conserved role in ribosome biosynthesis 4. Clinically, GNL3L is significantly upregulated in multiple cancers including lung adenocarcinoma and esophageal cancer, where it promotes proliferation, migration, and invasion through NF-κB pathway activation and upregulation of Slug, MMP2, and MMP9 56. High GNL3L expression correlates with poor prognosis in esophageal cancer 6. Conversely, GNL3L knockdown alleviates COPD progression through ATM/p53 pathway inhibition 7, suggesting therapeutic potential in cancer and chrX inflammatory diseases.