2018). In more proximal segments (PCT and TALH) the absence of αβ–FXYD2 interactions should also lead to reduced Na,K‐ATPase activity and lowered Mg reabsorption but, as with digoxin, this will not be fully compensated by increased Mg uptake in DCT. The paradox of activated NCC and NKCC2 in FXYD2−/− mice, without renal Na retention and hypertension (Arystarkhova et al. 2014), could then be considered, most simply, a compensatory mechanism for reduced Na reabsorption in more proximal segments (one possibility suggested in Arystarkhova et al. 2014). Here, FXYD2 is linked to hypertensive disorder.