Maintenance of lipid asymmetry across the two leaflets of the plasma membrane (PM) bilayer is a ubiquitous feature of eukaryotic cells. Loss of this asymmetry has been widely associated with cell death. However, increasing evidence points to the physiological importance of non-apoptotic, transient changes in PM asymmetry. Such transient scrambling events are associated with a range of biological functions, including intercellular communication and intracellular signaling. Thus, regulation of interleaflet lipid distribution in the PM is a broadly important but underappreciated cellular process with key physiological and structural consequences. Here, we compile the mounting evidence revealing multifaceted, functional roles of PM asymmetry and transient loss thereof. We discuss the consequences of reversible asymmetry on PM structure, biophysical properties and interleaflet coupling. We argue that despite widespread recognition of broad aspects of membrane asymmetry, its importance in cell biology demands more in-depth investigation of its features, regulation, and physiological and pathological implications.

质膜（PM）双层的两个小叶之间脂质不对称的维持是真核细胞的普遍特征。这种不对称性的丧失与细胞死亡广泛相关。然而，越来越多的证据表明 PM 不对称性的非凋亡、短暂变化具有生理重要性。这种短暂的扰乱事件与一系列生物功能相关，包括细胞间通讯和细胞内信号传导。因此，PM 中小叶间脂质分布的调节是一个广泛重要但未被充分认识的细胞过程，具有关键的生理和结构后果。在这里，我们汇编了越来越多的证据，揭示了 PM 不对称性及其瞬时损失的多方面功能作用。我们讨论了可逆不对称性对 PM 结构、生物物理特性和叶间耦合的影响。我们认为，尽管膜不对称性的广泛方面已得到广泛认可，但其在细胞生物学中的重要性需要对其特征、调节以及生理和病理影响进行更深入的研究。