Nucleostemin (NS), also known as guanine nucleotide-binding protein-like 3 (GNL3), is a nucleolar GTP-binding protein predominantly found in the nucleoli of stem cells, transformed cell lines, and various tumor cells. Initially identified in rat neural stem cells, NS is highly conserved across species and plays a crucial role in cell-cycle progression. It regulates cell proliferation by modulating ribosomal biogenesis and interacting with the p53-MDM2 feedback loop. Interestingly, both overexpression and depletion of NS can activate p53, suggesting its dual role in cellular homeostasis. Additionally, NS levels decrease as cells differentiate, making it a potential marker for stem cells and cancer cells. Its unique functions in ribosome assembly and cell-cycle regulation highlight its importance in both normal development and tumorigenesis.