The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities

The nucleolus has emerged as a dynamic and multifunctional subnuclear organelle that integrates ribosome biogenesis with cellular growth and stress signalling. Dysregulation of nucleolar function is increasingly recognised as a central driver of human disease, linking altered ribosome production and nucleolar surveillance pathways to cancer, ribosomopathies, premature ageing syndromes, neurodegeneration, and immune disorders. In this review, we integrate structural, molecular, and disease-level perspectives on nucleolar biology to define how ribosome biogenesis and nucleolar surveillance regulate cellular state across physiological and pathological contexts, positioning the nucleolus as an active regulator of cell function. We outline areas of convergence, identify key unresolved questions, and highlight therapeutic vulnerabilities that arise, including opportunities for small-molecule inhibitors and gene-based approaches.