Nucleophosmin (NPM1) is a mostly nucleolar protein with crucial functions in cell growth and homeostasis, including regulation of ribosome biogenesis and stress response. Such multiple activities rely on its ability to interact with nucleic acids and with hundreds of proteins, as well as on a dynamic subcellular distribution. NPM1 is thus regulated by a complex interplay between localization and interactions, further modulated by post-translational modifications. NPM1 is a homopentamer, with globular domains connected by long, intrinsically disordered linkers. This configuration allows NPM1 to engage in liquid-liquid phase separation phenomena, which could underlie a key role in nucleolar organization. Here, we will discuss NPM1 conformational and functional versatility, emphasizing its emerging, and still largely unexplored, role in DNA damage repair. Since NPM1 is altered in a subtype of acute myeloid leukaemia (AML), we will also present ongoing research on the molecular mechanisms underlying its pathogenic role and potential NPM1-targeting therapeutic strategies.

核蛋白（NPM1）是一种主要为核仁蛋白，在细胞生长和体内稳态（包括调节核糖体生物发生和应激反应）中起关键作用。这样的多种活动取决于其与核酸和数百种蛋白质相互作用的能力，以及动态的亚细胞分布。因此，NPM1由定位和相互作用之间的复杂相互作用调节，并由翻译后修饰进一步调节。NPM1是同型五聚体，球状结构域由长的固有无序的连接子连接。这种配置允许NPM1参与液-液相分离现象，这可能是核仁组织中的关键作用。在这里，我们将讨论NPM1的构象和功能通用性，强调其新兴的，但仍未开发的地方，在DNA损伤修复中的作用。由于NPM1在急性髓细胞性白血病（AML）的亚型中发生了改变，因此我们还将介绍有关其致病作用的分子机制和潜在的NPM1靶向治疗策略的正在进行的研究。