Once considered unconventional cellular structures, membraneless organelles (MLOs), cellular substructures involved in biological processes or pathways under physiological conditions, have emerged as central players in cellular dynamics and function. MLOs can be formed through liquid-liquid phase separation (LLPS), resulting in the creation of condensates. From neurodegenerative disorders, cardiovascular diseases, aging, and metabolism to cancer, the influence of MLOs on human health and disease extends widely. This review discusses the underlying mechanisms of LLPS, the biophysical properties that drive MLO formation, and their implications for cellular function. We highlight recent advances in understanding how the physicochemical environment, molecular interactions, and post-translational modifications regulate LLPS and MLO dynamics. This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases. This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research, highlighting their critical role in cellular organization. The discussion also covers the role of membrane-associated condensates in cell signaling, including those involving T-cell receptors, stress granules linked to lysosomes, and biomolecular condensates within the Golgi apparatus. Additionally, the potential of targeting LLPS in clinical settings is explored, highlighting promising avenues for future research and therapeutic interventions.

无膜细胞器 （MLO） 是生理条件下参与生物过程或通路的细胞亚结构，曾经被认为是非常规的细胞结构，现已成为细胞动力学和功能的核心参与者。MLO 可以通过液-液相分离 （LLPS） 形成，从而产生冷凝物。从神经退行性疾病、心血管疾病、衰老和新陈代谢到癌症，MLO 对人类健康和疾病的影响范围很广。本综述讨论了 LLPS 的潜在机制、驱动 MLO 形成的生物物理特性及其对细胞功能的影响。我们重点介绍了在了解物理化学环境、分子相互作用和翻译后修饰如何调节 LLPS 和 MLO 动力学方面的最新进展。这篇综述概述了 MLO 和生物分子凝聚物在生理条件和疾病中的发现和当前理解。本文旨在通过分析当前研究来提供有关 MLO 和 LLPS 的最新见解，强调它们在细胞组织中的关键作用。讨论还涵盖了膜相关凝聚物在细胞信号传导中的作用，包括涉及 T 细胞受体、与溶酶体相连的应激颗粒以及高尔基体内的生物分子凝聚物。此外，还探讨了在临床环境中靶向 LLPS 的潜力，突出了未来研究和治疗干预的有希望的途径。