To test our hypothesis, we and other laboratories have used novel mutant mouse models with whole body- (Schultheis et al., 1998a,b; Lorenz et al., 1999; Wang et al., 1999; Wang et al., 2001; Li et al., 2015b), kidney- (Woo et al., 2003; Noonan et al., 2005; Li et al., 2015a, 2019b; Fenton et al., 2017; Zhuo et al., 2021), or proximal tubule-specific deletion of NHE3 to study the important roles and underlying mechanisms of NHE3 in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension (Li et al., 2018, 2019b; Zhuo et al., 2021). This evidence concerns the gene SLC9A3 and hypertensive disorder.