As proof-of-concept studies, gastrointestinal NHE3 inhibitors have been developed to treat several disease targets including hypertension, constipation, and hyperphosphatemia in elder patients (Linz et al., 2012, 2016, 2020; Li et al., 2019b; Kovesdy et al., 2021). This evidence concerns the gene SLC9A3 and hyperphosphatemia.