WNK2 is a serine/threonine protein kinase that functions as a critical regulator of electrolyte homeostasis and cell signaling. As the upstream component of the WNK2-SPAK/OSR1 kinase cascade, WNK2 phosphorylates and activates downstream kinases OXSR1 and SPAK, which then regulate ion cotransporters controlling sodium and potassium-chloride transport 1. WNK2 negatively regulates ERK/MAPK pathway activation by modulating PAK1 activity through control of RHOA and RAC1 balance, thereby suppressing cell cycle progression 23. WNK2 functions as a tumor suppressor gene with inactivation occurring through promoter methylation and frameshift mutations in various cancers. In gliomas, WNK2 silencing increases Rac1 activation and upregulates MMP2 and JNK, promoting cell invasion and proliferation 45. WNK2 also inhibits autophagic flux through mTOR-independent mechanisms in glioblastoma 6. Beyond oncology, WNK2 serves as a PAX6 downstream target essential for corneal epithelial cell differentiation and homeostasis; its downregulation impairs corneal integrity 7. Germline WNK2 variants have been associated with serrated polyposis syndrome pathogenesis 8. Genetic polymorphisms in WNK2 influence prognosis in intracerebral hemorrhage patients receiving Edaravone treatment 9, suggesting clinical utility in personalized medicine approaches.