Although the contemporary view on how Na+ accumulation leads to NFAT5 activation in these tissues has been challenged recently (Rossitto et al., 2020), there is evidence suggesting that dysregulation of NFAT5 contributes to the pathogenesis of autoimmune diseases (Matthias et al., 2019; Aramburu and López-Rodríguez, 2019; Lee et al., 2019; Kleinewietfeld et al., 2013), inflammation (Aramburu and López-Rodríguez, 2019), hypertension and metabolic disorders (Jantsch et al., 2014). This evidence concerns the gene NFAT5 and autoimmune disease.