The protein kinase superfamily contains over a thousand proteins in 57 subfamilies that all share a catalytic core of 250C300 amino acids organized in two domains. WNK kinases (With No lysine (K)) are serine-threonine protein kinases that contain a cysteine residue in place of a lysine residue in a family of proteins that traditionally contain a lysine following a short string of hydro-phobic residues. WNK kinases contain a lysine upstream of the traditional position, within a glycine string. This lysine functions as an anchor and orients ATP through interactions with the alpha and beta phosphoryl groups. The catalytic domains of WNK2, WNK3 and WNK4 are 95% homologous to WNK1. Human WNK1 maps to chromosome 12p13 and encodes a 2382 protein that is primarily expressed in heart, kidney, muscle and distal nephron. Human WNK3 maps to chromosome Xp11.21-p11.23 and encodes a protein that is primarily expressed in brain. Human WNK4 maps to chromosome 17q21-q22 and encodes a 1243 amino acid protein that is expressed in kidney.