Vrk2, a serine/threonine kinase, belongs to the dark kinome. It codes for two isoforms, with the main one (Vrk2A) mainly in the cytoplasm, anchored to membranes like endoplasmic reticulum, mitochondria, and nuclear envelope. Vrk2 is involved in regulating apoptosis, nuclear membrane organization, immune responses, and Cajal bodies, and interacts with signaling modules on scaffold proteins to block regulatory signaling pathways [1].

In genetic studies, Vrk2 -/- mice showed depressive-like behaviors, suggesting its role in mood-related regulation [2]. Also, vrk2 -/- female zebrafish exhibited aggressive behavior, indicating its potential role in regulating social behaviors [3]. In cancer research, VRK2 promotes pancreatic cancer progression by activating the TNFα/NF-κB signaling pathway [4]. VRK2 is also associated with psychiatric and neurological disorders as multiple SNPs within or near VRK2 gene are correlated with illnesses like schizophrenia and major depressive disorder [5]. VRK2 inhibition can synergize with PD-1 blockade to enhance T cell-mediated anti-tumor immunity [6].

In conclusion, Vrk2 is involved in a variety of biological processes, from cell-related functions like apoptosis and immune responses to more complex behaviors such as mood-related and social behaviors. Its role in cancer and neurological/psychiatric diseases makes it an important gene for research. Gene knockout models in mice and zebrafish have been crucial in revealing these functions, providing insights into potential therapeutic strategies for related diseases.