紧密连接 (TJ) 是上皮细胞和内皮细胞的屏障，以维持胞间底物运输和细胞极性。作为邻近细胞膜的TJ胞浆结合蛋白，顶网蛋白 (ZO) 在连接跨膜TJ蛋白和胞质细胞骨架方面起着重要作用，为跨膜TJ蛋白提供一个结合平台，以维护屏障功能。除了基本的结构功能外，ZO蛋白在信号调控方面也发挥着重要作用，如细胞增殖和运动，后者包括细胞迁移、侵袭和转移，影响着胚胎发育、组织稳态、损伤修复、炎症、肿瘤发生和癌症进展。在本综述中，我们将重点关注ZO蛋白在炎症和肿瘤发生中的信号调控功能，并讨论以前研究的局限性以及ZO蛋白研究的未来挑战。©作者

Tight junction (TJ) is the barrier of epithelial and endothelial cells to maintain paracellular substrate transport and cell polarity. As one of the TJ cytoplasmic adaptor proteins adjacent to cell membrane, zonula occludens (ZO) proteins are responsible for connecting transmembrane TJ proteins and cytoplasmic cytoskeleton, providing a binding platform for transmembrane TJ proteins to maintain the barrier function. In addition to the basic structural function, ZO proteins play important roles in signal regulation such as cell proliferation and motility, the latter including cell migration, invasion and metastasis, to influence embryonic development, tissue homeostasis, damage repair, inflammation, tumorigenesis, and cancer progression. In this review, we will focus on the signal regulating function of ZO proteins in inflammation and tumorigenesis, and discuss the limitations of previous research and future challenges in ZO protein research.© The author(s).