“…To learn more about the involvement of NHE1 in gastrointestinal growth and differentiation, absorption and secretion, in barrier function and microbiome regulation would be of importance, given the fact that NHE1 inhibition is discussed as a strategy for curbing tumor growth and/or its invasive properties in a large variety of organs and tumor cell types ( Stock et al, 2012 ; Harguindey et al, 2013 ; Meehan et al, 2017 ; Guan et al, 2018 ; Hyun et al, 2019 ; Iorio et al, 2020 ; Tamtaji et al, 2020 ; Greco et al, 2021 ; Mo et al, 2021 ), as well as for organ protection during ischemia ( Jung et al, 2006 ; Lee et al, 2009 ; Doods and Wu, 2013 ; Karmazyn, 2013 ; Wu et al, 2013 ; Sasamori et al, 2014 ), and as an anti-inflammatory and barrier-protective strategy ( Khan et al, 2005 ; Farkas et al, 2010 ; Wu and Qi, 2012 ; Yang et al, 2013 ; Monet et al, 2016 ; Zhang et al, 2018 ; Dubaniewicz et al, 2021 ). However, the recent advancement in the generation and maintenance of epithelium-derived organoids from all gastrointestinal organs with preservation of their organ- and site specific function ( Co et al, 2021 ; Gómez and Boudreau, 2021 ; Jantaree et al, 2021 ; Puschhof et al, 2021 ; Shiota et al, 2021 ), now opens an avenue to learn more about the role of NHE1 in the development and differentiation pattern of gastrointestinal epithelial cells, about its involvement in transepithelial transport of nutrients and electrolytes, and about its importance in microbial resistance and barrier function. First studies are published that demonstrate a differential expression of acid/base transporters along with absorptive or secretory ion channels or exchangers during the differentiation of human ( Yin et al, 2018 ; Zomer-van Ommen et al, 2018 ; Zhou et al, 2021 ) or mouse ( Nikolovska et al, 2022 ) intestinal organoids.…”