The Na⁺/K⁺-ATPase is an integral plasma membrane protein found in animal cells that drives the exchange of three intracellular Na⁺ ions for two K⁺ ions using energy from each ATP molecule hydrolysis [1]. Although crystal structures of the Na⁺ pump have been reported, they do not fully explain ion pump regulation at the molecular level in vivo. Domains absent from current structures are thought to play critical regulatory roles, making them promising targets to study. Based on the group’s recent findings, it was proposed that the Na+ pump interacts with the cytoplasmic face of their surrounding membrane via their lysine-rich positively charged N-termini [2-4]. The N-termini are electrostatically attracted to the negatively charged lipid headgroups exclusively located on the cytoplasmic face of the membrane [5, 6]. Hence, the rate of the enzyme’s E2→E1 (slowest step) conformational change strongly depends on such electrostatic interaction in the E2 state, which must be broken to allow it to convert to its Na+ specific E1 state [6]. The extent of this interaction depends on ionic strength and the concentration of divalent metal ions like Ca2+ and Mg2+ [7]. It has also been proposed that phosphorylation of serine and/or tyrosine residues in the N-termini by protein kinase C or Src kinase introduces negative charges that weaken membrane interactions, thereby modulating pump activity [8]. Results from the Surface Electrogenic Event Reader (SURFE2R), that measured capacitive currents within membranes adsorbed to a hybrid solid supported membrane (SSM), showed that Ca²⁺ binds to lipid membranes, with enhanced binding in the presence of Na⁺ pump containing membrane fragments. This suggests the possibility of Ca2+ having a signaling role in Na+ pump activity. Further comparative studies with the N-terminally truncated Na+ pump variants enables assessment of the role of the N-terminus in regulating ion pump activity.