DYRK3, short for dual-specificity tyrosine-phosphorylation-regulated kinase 3, is a member of the DYRK family. It plays crucial roles in multiple biological processes. It is involved in pathways such as secretory trafficking, where it maintains the liquid-like state of ER exit sites (ERESs) to enable proper cargo trafficking through the early secretory pathway [1]. It also participates in regulating axonal retrograde transport, neurotransmitter release, cell migration, and is associated with processes like erythropoiesis, stress granule disassembly, and cancer-related pathways [3,4,5,7].

In DYRK3 knockout mice, erythropoiesis is enhanced during anemia, indicating that DYRK3 normally attenuates red cell production in such conditions [7]. In the context of oral squamous cell carcinoma (OSCC), inhibiting DYRK3 can disrupt purinosome formation and influence the survival rate of radiation-resistant OSCC cell lines, suggesting its role in radiotherapy resistance [2]. In glioblastoma, knockdown of DYRK3 inhibits mitochondrial fission, leading to increased oxidative phosphorylation and reduced glycolysis, and impairs cell migration and invasion [6]. In melanoma, DYRK3 knockdown or blockade of its phosphorylation of p62 at Thr-269 inhibits melanoma growth, colony formation, and cell migration [8].

In conclusion, DYRK3 is essential in regulating diverse biological functions including cell trafficking, neuronal functions, and cell growth. Gene knockout models have revealed its significant roles in diseases such as anemia, various cancers including OSCC, glioblastoma, and melanoma. Understanding DYRK3 through these models provides insights into disease mechanisms and potential therapeutic strategies for these conditions.