MAD2L2, also known as REV7, is a small HORMA domain protein that plays crucial roles in DNA repair, mitosis, and tumor-related processes. It is part of the shieldin complex, which controls DNA repair pathway choice by counteracting DNA end-resection. MAD2L2 is also involved in protecting stalled replication forks and maintaining genomic stability [1,2].

In genetic studies, MAD2L2 knockout cells have been used to explore its functions. In mitosis, MAD2L2 can function in its monomeric form as dimer-disrupting point mutations in MAD2L2 generated by Nuclease technology did not disrupt early mitotic regulation, suggesting that homodimerization is dispensable for mitotic regulation [4]. In glioma, silencing MAD2L2 in vitro and in vivo decreased the proliferation, invasion, and migration of glioblastoma cells and the stemness characteristics of glioblastoma stem cells, indicating its promoting role in glioma progression [3]. In lung adenocarcinoma, down-regulation of the HNRNPD/MAD2L2 axis inhibited tumor progression in vitro and in vivo, while up-regulation facilitated it, showing its significance in lung adenocarcinoma [5].

In conclusion, MAD2L2 is essential for DNA repair, replication fork protection, and mitotic regulation. Its dysregulation is associated with various cancers such as glioma, lung adenocarcinoma, ovarian cancer, and bladder cancer. Studies using gene knockout models have revealed its key functions in these biological processes and disease conditions, providing insights into potential therapeutic targets for cancer treatment.