NhaA Na⁺:2H⁺ antiporter (structure determined and mechanism proposed (Williams, 2000; Hunte et al., 2005; Olkhova et al., 2006; Screpanti et al., 2006; Arkin et al., 2007)). The K300R mutant is also electrogenic (Călinescu et al. 2017).  TMS II lines the cation passage, and Asp65 is critical for pH activation of the antiporter (Herz et al., 2010). NhaA is subject to pH-activation of the ion-translocating conformation (Appel et al., 2009; Diab et al., 2011). A periplasm-facing state of the NhaA antiporter suggests the molecular underpinnings of the pH-induced conformational changes (Schushan et al., 2012).  A central unwound part of TMS IV appears to line the cation passage channel (Rimon et al. 2012).  TMSs VI and VII are absent from many homologues, are not required for transport or its regulation and function in assembly and stability (Padan et al. 2015). pH-induced conformational changes have been documented (Kozachkov et al. 2007).  Two acidic residues in the binding site that carries the protons in electrogenic CPAs, and a polar residue in the unwound transmembrane helix 4 that determines ion selectivity have been identified. A rationally designed triple mutant successfully converted the electrogenic EcNhaA, to be electroneutral (Masrati et al. 2018). Residues involved in NhaA function have been reviewed (Dwivedi 2020).  The type of residues involved in substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilieshave been reviewed (Patiño-Ruiz et al. 2022). Several aspects of prokaryotic Na⁺/H⁺ exchanger structures and function are presented, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers (Patiño-Ruiz et al. 2022).