VRK2, or vaccinia-related kinase 2, is a serine/threonine kinase. It is involved in multiple biological processes such as cell proliferation, survival, and apoptosis. VRK2 also plays a role in regulating signaling pathways like TNFα/NF-κB, and is associated with various cellular functions including nuclear membrane organization, immune responses, and Cajal bodies regulation [2]. Genetic models, like gene knockout models, have been valuable in studying VRK2's functions.

VRK2-deficient zebrafish showed aggressive behavior in females, with low gamma-aminobutyric acid (GABA) content in the brain [3]. In mice, Vrk2-/-mice exhibited depressive-like behaviors, and repressing Vrk2 in the ventral hippocampus led to similar phenotypes, along with altered spine density and dysregulated synapse-associated proteins [4]. In VRK2-null or VRK2-methylated glioblastoma cells, knockdown of VRK1 (a paralog of VRK2) led to decreased activity of the downstream substrate BAF, causing nuclear abnormalities, G2-M arrest, and DNA damage [1,5].

In conclusion, VRK2 is crucial in various biological processes. Model-based research, especially gene knockout in zebrafish and mice, has revealed its significance in neuropsychiatric disorders like aggression and depression. In cancer, the relationship between VRK2 and its paralog VRK1 shows potential therapeutic implications for glioblastoma [1,3,4,5].

References:

1. Shields, Julie A, Meier, Samuel R, Bandi, Madhavi, Huang, Alan, Emmanuel, Natasha. . VRK1 Is a Synthetic-Lethal Target in VRK2-Deficient Glioblastoma. In Cancer research, 82, 4044-4057. doi:10.1158/0008-5472.CAN-21-4443. https://pubmed.ncbi.nlm.nih.gov/36069976/

2. Lazo, Pedro A. 2025. VRK2 kinase pathogenic pathways in cancer and neurological diseases. In Biochimica et biophysica acta. Molecular cell research, 1872, 119949. doi:10.1016/j.bbamcr.2025.119949. https://pubmed.ncbi.nlm.nih.gov/40187568/

3. Umeda, Ryohei, Teranishi, Hitoshi, Hada, Kazumasa, Hanada, Toshikatsu, Hanada, Reiko. 2022. Vrk2 deficiency elicits aggressive behavior in female zebrafish. In Genes to cells : devoted to molecular & cellular mechanisms, 27, 254-265. doi:10.1111/gtc.12924. https://pubmed.ncbi.nlm.nih.gov/35094457/

4. Yin, Mei-Yu, Guo, Lei, Zhao, Li-Juan, Wang, Chuang, Chang, Hong. 2023. Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice. In BMC medicine, 21, 256. doi:10.1186/s12916-023-02945-0. https://pubmed.ncbi.nlm.nih.gov/37452335/

5. So, Jonathan, Mabe, Nathaniel W, Englinger, Bernhard, Filbin, Mariella G, Hahn, William C. 2022. VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system. In JCI insight, 7, . doi:10.1172/jci.insight.158755. https://pubmed.ncbi.nlm.nih.gov/36040810/