Sun2, also known as SAD1/UNC84 domain protein-2, is a nuclear membrane protein that plays diverse and crucial roles. It is a component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, which tethers the cell nucleus to the cytoskeleton, regulating mechanical forces during cell migration, differentiation, etc. It also has functions related to maintaining cell nuclear structure, organizing the natural nuclear architecture in cancer cells, and is involved in processes like gene expression regulation [3,6].

In cancer, Sun2 acts as a tumor suppressor. FBXO2, an E3 ubiquitin ligase, targets glycosylated Sun2 for ubiquitination and degradation via the ubiquitin-proteasome system, promoting ovarian cancer development. This discovery of the SOX6-FBXO2-Sun2 axis suggests targeting this axis could be an effective ovarian cancer treatment strategy [1]. In flavivirus replication, CRISPR/Cas9-mediated knockout of Sun2 significantly reduces the replication of Zika virus, dengue virus, and Japanese encephalitis virus, indicating its role in facilitating cytoskeleton rearrangement and viral replication organelle formation [2]. In HSV-1 propagation, disruption of Sun2 leads to increased extracellular viral yields, showing its antiviral property [4]. In response to extracellular matrix rigidity, Sun2 expression is regulated. High Sun2 levels on rigid substrates promote metaphase-to-anaphase transition by acting on mitotic spindle formation, while low levels on soft substrates delay anaphase onset [5].

In conclusion, Sun2 is a multifunctional protein with key roles in cancer suppression, viral replication, and cell division regulation. The gene knockout studies have been instrumental in revealing its functions in these biological processes and disease conditions, providing potential therapeutic targets for cancer and insights into viral-host interactions.