NOLC1 is a nucleolar phosphoprotein that functions as a regulatory adaptor connecting RNA polymerase I with ribosomal processing and modification enzymes 12. It contains intrinsic GTPase and ATPase activities and plays essential roles in nucleologenesis and maintaining nucleolar structure 3. Beyond its core ribosomal functions, NOLC1 regulates neural crest specification through monoubiquitination by the BCR(KBTBD8) complex, where it associates with TCOF1 to remodel translational programs 2. Clinically, NOLC1 exhibits complex roles in disease. In thyroid cancer, NOLC1 functions as a tumor suppressor, with expression correlating to patient prognosis 4. Conversely, in endometrial cancer, NOLC1 accumulation following SPOP mutations promotes paclitaxel resistance by activating B4GALT1-mediated abnormal glycosylation 5. In gastric cancer, NOLC1 suppresses p53-mediated ferroptosis and immunotherapy sensitivity by binding p53's DNA-binding domain 6. NOLC1 also represents a newly identified autoantigen in systemic sclerosis patients 7. Recent proteomic evidence reveals NOLC1 undergoes extensive pyrophosphorylation via inositol pyrophosphates, affecting rDNA transcription 8. Additionally, NOLC1 functions within snoRNA ribonucleoprotein complexes to regulate snoRNA-target interactions in ribosome and spliceosome biogenesis 9.