PAK2, a serine-threonine kinase, is a member of the p21-activated kinase (PAK) family. It is activated by GTP-bound rho family GTPases, Rac, and Cdc42, and is involved in regulating actin dynamics, cell adhesion, and cell motility. PAK2 participates in multiple signaling pathways, such as those related to pancreatic acinar cell function, cancer-related processes, and myelination [1,2,3,4]. Genetic models, like knockout mouse models, are valuable for studying its functions.

In pancreatic acinar cells, inhibition of PAK2 using IPA-3, FRAX597, or a PAK2-dominant negative-Advirus suppressed the activation of certain signaling cascades, protected against early pancreatitis events like ROS-generation, caspase/trypsin-activation, and cell-necrosis [1]. In Schwann cell-specific Pak2 knockout mice (scPak2-/ -), severe hypomyelination, slowed nerve conduction velocity, and behavior dysfunctions occurred, indicating PAK2 is necessary for myelination in the peripheral nervous system [4]. In mouse oocytes, depletion of Pak2 led to metaphase I arrest and meiotic chromosome alignment defects, suggesting its importance in meiotic progression [5]. In Th17 cells, genetic deletion of Pak2 reduced RORγt phosphorylation, increased IL-17 expression, and induced severe colitis [6].

In conclusion, PAK2 is crucial for multiple biological processes. Its roles in pancreatic acinar cell signaling and the onset of pancreatitis, myelination in the peripheral nervous system, oocyte meiotic progression, and regulation of colonic inflammation are revealed through gene-knockout-based research. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets for conditions like pancreatitis, peripheral neuropathies, and inflammatory bowel diseases.