LYAR (Ly1 antibody reactive) is a multifunctional nucleolar and nuclear protein with roles in ribosome biogenesis, transcriptional regulation, and immune control. Mechanistically, LYAR accelerates pre-rRNA processing from 47S/45S to 32S/30S intermediates, ultimately producing mature 18S and 28S rRNAs 1. Beyond ribosome biogenesis, LYAR functions as a DNA-binding transcription factor preferentially recognizing 5'-GGTTAT-3' motifs 2. It represses γ-globin expression through PRMT5-dependent histone modifications and suppresses oxidative stress genes in neuroblastoma, including CHAC1, by recruiting PRMT5 to target promoters 23. LYAR negatively regulates innate immunity by impairing IRF3 DNA-binding activity and inhibiting NF-κB-mediated cytokine expression 4. In intestinal stem cells, nucleolar LYAR sequestration by Snora54 prevents Notch2 promoter activation and maintains quiescence; Snora54 loss liberates LYAR to the nucleoplasm, promoting Notch2 transcription and self-renewal 5. Clinically, LYAR upregulation in colorectal cancer, neuroblastoma, and non-small cell lung cancer correlates with poor prognosis and enhanced proliferation 637. LYAR also facilitates influenza A virus replication by promoting viral RNP assembly 8.