WNK463 is a potent and selective inhibitor of the With-No-Lysine (WNK) kinase family, particularly targeting WNK1 and WNK4. It is primarily used in research settings to study the role of WNK signaling pathways in ion transport and cellular homeostasis. Due to its ability to modulate the activity of downstream kinases such as SPAK and OSR1, WNK463 effectively inhibits the Na+-K+-2Cl− cotransporter (NKCC) and the Na+-Cl− cotransporter (NCC), making it a valuable tool for investigating electrolyte balance and blood pressure regulation. Its application extends to studying diseases related to WNK pathway dysregulation, such as pseudohypoaldosteronism type II (PHAII), a rare genetic disorder characterized by hypertension and hyperkalemia. WNK463 has also shown potential in preclinical models for treating hypertension and certain types of cancer where WNK kinases contribute to cell proliferation and survival. By blocking aberrant WNK signaling, it helps elucidate therapeutic strategies for conditions involving ion transport dysfunction.