Tight junctions (TJs) are intercellular junctions critical for building the epithelial barrier and maintaining epithelial polarity. The claudin family of membrane proteins play central roles in TJ structure and function. However, recent findings have uncovered claudin-independent aspects of TJ structure and function, and additional players including junctional adhesion molecules (JAMs), membrane lipids, phase separation of the zonula occludens (ZO) family of scaffolding proteins, and mechanical force have been shown to play important roles in TJ structure and function. In this review, we discuss how these new findings have the potential to transform our understanding of TJ structure and function, and how the intricate network of TJ proteins and membrane lipids dynamically interact to drive TJ assembly.

紧密连接（TJ）是细胞间连接，对于建立上皮屏障和维持上皮极性至关重要。膜蛋白的claudin家族在TJ结构和功能中起着核心作用。但是，最近的发现发现了TJ结构和功能的非claudin依赖性方面，并且还显示了其他参与者，包括结缔黏附分子（JAM），膜脂，小腿闭合蛋白（ZO）支架蛋白家族的相分离以及机械力在TJ结构和功能中扮演重要角色。在这篇综述中，我们讨论了这些新发现如何可能改变我们对TJ结构和功能的理解，以及TJ蛋白和膜脂质的复杂网络如何动态相互作用以驱动TJ组装。