Fields of particular interest include first, a further elucidation of the ion–water disbalance upon excessive neutrophil activation, second, an in-depth evaluation of physiological parameters, including intracellular pH and cellular size of neutrophils as a diagnostic and/or prognostic marker of immune dysfunction, and third, a meaningful translation to the bedside by modulating ion–water based alterations, for example, by pharmacological targeting of perpetrator ion transport proteins, such as NHE1, during sepsis. This evidence concerns the gene SLC22A23 and Sepsis.