Calcineurin is a calcium-dependent serine–threonine protein phosphatase. Calcineurin activates the nuclear factor of activated T-cells cytoplasmic (NFAT) c, a transcription factor, by dephosphorylating the protein. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of T-cell responses. Calcineurin is the target of a drug class called calcineurin inhibitors (CNI), which includes cyclosporine and tacrolimus. The NFAT transcription factor family consists of five members NFATc1, NFATc2, NFATc3, NFATc4 and NFAT5. Calcium signalling regulates NFATc1—NFATc4. In T cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. The tacrolimus macrolide prevents the dephosphorylation of NFAT by binding to the immunophilin, FK506 binding protein, thereby creating a new complex that reduces peptidylprolyl isomerase activity. This complex inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.

Pseudohypoaldosteronism type II (PHA-II) or familial hyperkalaemic hypertension (FHH) is a rare familial renal tubular defect characterized by hypertension and hyperkalaemic, non-anion gap metabolic acidosis in the presence of low renin and aldosterone levels. The molecular basis for most individuals who have PHA-II was linked to loss-of-function mutations in the ‘with-no-lysine’kinases (WNK), either WNK1 or WNK4. The WNK kinases comprise a family of serine–threonine protein kinases with unusual placement of the catalytic lysine compared with all other protein kinases. WNK1 or WNK4 regulate chloride cotransporters of the distal nephron and other epithelia. The WNK kinase network and how it regulates sodium balance, potassium homeostasis and blood pressure has recently been reviewed [1, 2].