The eukaryotic plasma membrane's lipid composition is found to be ubiquitously asymmetric comparing inner and outer leaflets. This membrane lipid asymmetry plays a crucial role in diverse cellular processes critical for cell survival. A specialized set of transmembrane proteins called translocases, or flippases, have evolved to maintain this membrane lipid asymmetry in an energy-dependent manner. One potential consequence of local variations in membrane lipid asymmetry is membrane remodeling, which is essential for cellular processes such as intracellular trafficking. Recently, there has been a surge in the identification and characterization of flippases, which has significantly advanced the understanding of their functional mechanisms. Furthermore, there are intriguing possibilities for a coupling between membrane curvature and flippase activity. In this review we highlight studies that link membrane shape and remodeling to differential stresses generated by the activity of lipid flippases with an emphasis on data obtained through model membrane systems. We review the common mechanistic models of flippase-mediated lipid flipping and discuss common techniques used to test lipid flippase activity. We then compare the existing data on lipid translocation rates by flippases and conclude with potential future directions for this field.

与内叶和外叶相比，真核细胞质膜的脂质组成普遍不对称。这种膜脂不对称性在对细胞生存至关重要的多种细胞过程中起着至关重要的作用。一组称为易位酶或翻转酶的特殊跨膜蛋白已进化出以能量依赖性方式维持这种膜脂不对称性。膜脂不对称局部变化的一个潜在后果是膜重塑，这对于细胞内运输等细胞过程至关重要。最近，翻转酶的鉴定和表征激增，极大地促进了对其功能机制的理解。此外，膜曲率和翻转酶活性之间的耦合存在着有趣的可能性。在这篇综述中，我们重点介绍了将膜形状和重塑与脂质翻转酶活性产生的差异应力联系起来的研究，重点是通过模型膜系统获得的数据。我们回顾了翻转酶介导的脂质翻转的常见机制模型，并讨论了用于测试脂质翻转酶活性的常用技术。然后，我们比较翻转酶脂质易位率的现有数据，并得出该领域未来潜在方向的结论。