The nucleolus is the most prominent nuclear body and serves a fundamentally important biological role as a site of ribonucleoprotein particle assembly, primarily dedicated to ribosome biogenesis. Despite being one of the first intracellular structures visualized historically, the biophysical rules governing its assembly and function are only starting to become clear. Recent studies have provided increasing support for the concept that the nucleolus represents a multilayered biomolecular condensate, whose formation by liquid–liquid phase separation (LLPS) facilitates the initial steps of ribosome biogenesis and other functions. Here, we review these biophysical insights in the context of the molecular and cell biology of the nucleolus. We discuss how nucleolar function is linked to its organization as a multiphase condensate and how dysregulation of this organization could provide insights into still poorly understood aspects of nucleolus-associated diseases, including cancer, ribosomopathies and neurodegeneration as well as ageing. We suggest that the LLPS model provides the starting point for a unifying quantitative framework for the assembly, structural maintenance and function of the nucleolus, with implications for gene regulation and ribonucleoprotein particle assembly throughout the nucleus. The LLPS concept is also likely useful in designing new therapeutic strategies to target nucleolar dysfunction.

核仁是最突出的核体，作为核糖核蛋白颗粒组装位点发挥着重要的生物学作用，主要致力于核糖体的生物发生。尽管是历史上最早可视化的细胞内结构之一，但控制其组装和功能的生物物理规则才刚刚开始变得清晰。最近的研究为核仁代表多层生物分子凝聚物的概念提供了越来越多的支持，其通过液 - 液相分离（LLPS）的形成促进了核糖体生物发生和其他功能的初始步骤。在这里，我们在核仁的分子和细胞生物学背景下回顾了这些生物物理学见解。我们讨论了核仁功能如何与其作为多相凝聚物的组织相关联，以及该组织的失调如何提供对核仁相关疾病仍知之甚少的方面的见解，包括癌症、核糖体病和神经变性以及衰老。我们建议 LLPS 模型为核仁的组装、结构维持和功能提供统一的定量框架的起点，这对整个细胞核的基因调控和核糖核蛋白颗粒组装具有重要意义。LLPS 概念也可能有助于设计针对核仁功能障碍的新治疗策略。核糖体病和神经变性以及衰老。我们建议 LLPS 模型为核仁的组装、结构维持和功能提供统一的定量框架的起点，这对整个细胞核的基因调控和核糖核蛋白颗粒组装具有重要意义。LLPS 概念也可能有助于设计针对核仁功能障碍的新治疗策略。核糖体病和神经变性以及衰老。我们建议 LLPS 模型为核仁的组装、结构维持和功能提供统一的定量框架的起点，这对整个细胞核的基因调控和核糖核蛋白颗粒组装具有重要意义。LLPS 概念也可能有助于设计针对核仁功能障碍的新治疗策略。