蛋白激酶B（Akt）通路可以通过激活多个下游靶基因来调节肿瘤细胞和干细胞的生长、增殖和代谢，从而影响一系列疾病的发生和治疗。硫酯酶超家族成员 4 (THEM4) 是硫酯酶超家族的成员，是 Akt 激酶结合蛋白之一。一些关于癌症和其他疾病机制的研究表明，THEM4 与 Akt 结合来调节其磷酸化。最初，THEM4被认为是Akt的内源性抑制剂，可以在肺癌、胰腺癌、肝癌等疾病中抑制Akt的磷酸化，但随后，THEM4被证明可以通过正向调节Akt活性来促进肿瘤细胞的增殖在乳腺癌和鼻咽癌中，这与之前的发现相矛盾。考虑到这两种不同的观点，本文总结了THEM4在Akt通路中的重要作用，重点关注THEM4作为Akt结合蛋白及其在各种疾病，特别是癌症中与Akt磷酸化的调节关系。这项工作让人们更好地了解 THEM4 联合 Akt 在疾病治疗中的作用。

The protein kinase B (Akt) pathway can regulate the growth, proliferation, and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes, thus affecting the development and treatment of a range of diseases. Thioesterase superfamily member 4 (THEM4), a member of the thioesterase superfamily, is one of the Akt kinase-binding proteins. Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation. Initially, THEM4 was considered an endogenous inhibitor of Akt, which can inhibit the phosphorylation of Akt in diseases such as lung cancer, pancreatic cancer, and liver cancer, but subsequently, THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma, which contradicts previous findings. Considering these two distinct views, this review summarizes the important roles of THEM4 in the Akt pathway, focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases, especially cancer. This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.