Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] By hypertonicity (By similarity). Activation requires autophosphorylation of Ser-380, that may be regulated by calcium. Phosphorylation of Ser-376 also promotes increased activity (By similarity). Interacts with SYT2. Interacts with WNK3 and WNK4. Interacts with KLHL3. Autophosphorylation at Ser-380 is inhibited by intracellular calcium. Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a BCR(KLHL2) complex, leading to proteasomal degradation. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins. HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. However, it is most probably an alternative exon which has been also described in alternative splicing products of the human and mouse WNK1 genes. Isoforms bearing this exon are specifically expressed in the nervous system in these species. Probable cloning artifact.