Srpk2, or serine/arginine-rich protein kinase 2, is a key kinase involved in alternative splicing regulation [3,4,5]. It phosphorylates serine/arginine-rich proteins, which impacts pre-mRNA splicing, thus influencing various biological processes and disease-related pathways. It is associated with pathways like de novo lipogenesis, and has been linked to diseases such as Alzheimer's disease, alcohol-associated liver disease, and multiple types of cancer [2,3,5]. Genetic models, especially gene knockout models, are valuable for studying Srpk2's functions.

In HepG2 cells, SRPK2-knockout suppressed hepatitis B core protein (Cp) phosphorylation, indicating its importance in the HBV life cycle as it mediates Cp phosphorylation and capsid assembly [1]. In BV2 microglia, enhanced SRPK2 expression contributed to pro-inflammatory activation, and its deficiency alleviated cytotoxic effects on HT22 cells [2]. In alcohol-associated liver disease, SRPK2 is activated in hepatocytes, and its silencing rescues alcohol-induced splicing dysregulation and liver injury in FGF21 knockout mice, revealing its role in lipogenesis regulation in this disease [5].

In conclusion, Srpk2 plays essential roles in multiple biological processes such as viral capsid assembly, microglia activation, and lipogenesis. Gene knockout models have been crucial in uncovering its functions in diseases like HBV-related infections, Alzheimer's disease, and alcohol-associated liver disease, providing insights into potential therapeutic targets for these conditions.