GNL1 (G protein nucleolar 1) is a nucleolar GTPase belonging to the HSR1_MMR1 subfamily that functions as a critical regulator of cell proliferation and survival. Mechanistically, GNL1 promotes cell cycle progression through retinoblastoma protein hyperphosphorylation and interacts functionally with ribosomal protein S20 (RPS20) to modulate proliferation 1. Its subcellular localization is tightly regulated in a cell cycle-dependent manner: GNL1 localizes to the nucleus/nucleolus specifically during G2 phase via a novel arginine/lysine-rich nucleolar localization signal, with GTP binding critical for nucleolar retention and G2/M transition 2. GNL1 promotes cell survival through the PI3K/AKT/p21 signaling pathway, inhibiting apoptosis via modulation of Bcl2 family proteins and caspase cleavage, while also conferring chemotherapy resistance 3. Disease relevance includes association with tumorigenesis in colon and gastric cancers, where GNL1 and RPS20 expression inversely correlate with patient survival 1. Additionally, GNL1 binds RNA G-quadruplex structures in Parkinson's disease-associated genes (PRKN and VPS35), regulating their translation 4, and genetic variants in GNL1 are associated with gender-dependent risk of Graves' ophthalmopathy 5. GNL1 also contributes to enteric nervous system development, with epistatic interactions involving RET in Hirschsprung disease 6.