Ten-eleven translocation (TET) family proteins (TETs), specifically, TET1, TET2 and TET3, can modify DNA by oxidizing 5-methylcytosine (5mC) iteratively to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxycytosine (5caC), and then two of these intermediates (5fC and 5caC) can be excised and return to unmethylated cytosines by thymine-DNA glycosylase (TDG)-mediated base excision repair. Because DNA methylation and demethylation play an important role in numerous biological processes, including zygote formation, embryogenesis, spatial learning and immune homeostasis, the regulation of TETs functions is complicated, and dysregulation of their functions is implicated in many diseases such as myeloid malignancies. In addition, recent studies have demonstrated that TET2 is able to catalyze the hydroxymethylation of RNA to perform post-transcriptional regulation. Notably, catalytic-independent functions of TETs in certain biological contexts have been identified, further highlighting their multifunctional roles. Interestingly, by reactivating the expression of selected target genes, accumulated evidences support the potential therapeutic use of TETs-based DNA methylation editing tools in disorders associated with epigenetic silencing. In this review, we summarize recent key findings in TETs functions, activity regulators at various levels, technological advances in the detection of 5hmC, the main TETs oxidative product, and TETs emerging applications in epigenetic editing. Furthermore, we discuss existing challenges and future directions in this field.

10-11 易位 (TET) 家族蛋白 (TET)，特别是 TET1、TET2 和 TET3，可以通过反复氧化 5-甲基胞嘧啶 (5mC) 来修饰 DNA，产生 5-羟甲基胞嘧啶 (5hmC)、5-甲酰胞嘧啶 (5fC) 和5-羧基胞嘧啶 (5caC)，然后可以切除这些中间体中的两个（5fC 和 5caC），并通过胸腺嘧啶 DNA 糖基化酶 (TDG) 介导的碱基切除修复恢复为未甲基化的胞嘧啶。由于DNA甲基化和去甲基化在受精卵形成、胚胎发生、空间学习和免疫稳态等众多生物过程中发挥着重要作用，TET功能的调节非常复杂，其功能失调与许多疾病（例如骨髓恶性肿瘤）有关。此外，最近的研究表明TET2能够催化RNA的羟甲基化来进行转录后调控。值得注意的是，TET 在某些生物学背景下的催化独立功能已被确定，进一步凸显了它们的多功能作用。有趣的是，通过重新激活选定靶基因的表达，积累的证据支持基于 TET 的 DNA 甲基化编辑工具在与表观遗传沉默相关的疾病中的潜在治疗用途。在这篇综述中，我们总结了 TET 功能、各个水平的活性调节剂、5hmC（TET 主要氧化产物）检测的技术进展以及 TET 在表观遗传编辑中的新兴应用方面的最新关键发现。此外，我们讨论了该领域现有的挑战和未来的方向。