Mistargeting mutations in epithelial cells lead also to defective polarized trafficking to the apical or basolateral membranes, causing rerouting of the mutant protein to the incorrect membrane domain, as, for example, in distal renal tubular acidosis caused by mutations in the chloride-bicarbonate exchanger AE1 and aquaporin 2 disrupting their basolateral and apical targeting signals, respectively [38,44,45]. Here, AQP2 is linked to distal renal tubular acidosis.