WNK

WNK stands for With No Lysine kinases, a family of atypical serine/threonine protein kinases found in animals. They are defined by the absence of the conserved catalytic lysine in subdomain II of most kinases, hence the name. WNKs regulate electrolyte handling and cardiovascular physiology by modulating transporter activity and signaling pathways.

The principal members are WNK1, WNK2, WNK3, and WNK4. They are expressed in several tissues, with major roles in the kidney where they influence salt reabsorption in the distal nephron. WNK proteins activate downstream kinases SPAK and OSR1, which phosphorylate and regulate ion transporters.

In the kidney, WNK-SPAK/OSR1 signaling controls the Na-Cl cotransporter NCC and the Na-K-2Cl cotransporter NKCC2, as well as ROMK potassium channels. Through these targets, WNK pathways shape sodium balance, potassium excretion, and blood pressure.

Clinically, mutations in WNK1 or WNK4 cause pseudohypoaldosteronism type II (Gordon syndrome), a hereditary form of hypertension with hyperkalemia. The WNK pathway is linked to broader electrolyte disorders and blood pressure regulation, making it a focus of medical research.

Therapeutically, researchers investigate inhibitors of the WNK-SPAK/OSR1 axis to treat hypertension and edema. Experimental WNK inhibitors have shown reduced NCC activity in preclinical models. Ongoing work seeks selective agents with acceptable safety profiles.

Outside biology, WNK can appear as an acronym or designation in other fields, but the kinase family is the best-known use.