Three of the five top-ranked genes in the apical gene set were SLC9A3, SLC9A3R2 (MIM: 606553), and EZR (MIM: 123900), with ten genes in total displaying JLS-Fisher p < 0.05 (Table S4). Of these top five, protein product interactions are known between (1) SLC9A3 (also known as NHE3) and SLC9A3R2 (“SLC9A3 regulator 2,” also known as E3KARP or NHERF2), (2) SLC9A3 and EZR, and (3) SLC9A3R2 and EZR. SLC9A3R1, or “SLC9A3 regulator 1” (also known as EBP50 or NHERF1), is recognized as a paralog of SLC9A3R2 with comparable binding sites to both SLC9A3 and EZR (reviewed in Donowitz and Li30); SLC9A3R1 (MIM: 604990) was the 21st ranked. Based on interaction investigations typically involving intestinal and kidney tissues, a current paradigm is that EZR provides anchorages for the SLC9A3 regulators to the actin cytoskeleton, and probably also facilitates early trafficking of SLC9A3 from the Golgi to the cell periphery, with eventual “hand-off” to the SLC9A3 regulators. The SLC9A3 regulators help to maintain SLC9A3 at the apical membrane and facilitate its dynamic shuffling with endosomes and internal vesicles.30