“…In contrast, I propose that the salient commonality between the kidney and the LR axis is their tight linkage of cell polarization to ion transport localization. Kidney cells (and epithelial cells in general) are highly polarized, and exert strong control over ion fluxes by using cytoskeletal and motor protein transport elements to regulate the intracellular membrane transport of ion channels and pumps, specifically including the H þ and K þ transporters known to be important in asymmetry (Nelson et al, 1991;Brown et al, 1992;Nelson, 1992;Suzuki et al, 1995;Al-Awqati et al, 1999;Fujita et al, 2002;Yao et al, 2002;Beyenbach, 2001). Other components implicated in LR asymmetry, such as claudins are also involved in kidney function (Yu et al, 2003;Abuazza et al, 2006;Balkovetz, 2006;Gonzalez-Mariscal et al, 2006;Lee et al, 2006), as they shape the transepithelial voltage gradients resulting from the targeted ion flows.…”