Epithelial brush borders in the intestine and kidneys are involved in essential absorptive processes. The brush-border (BB) Na+-H+ exchanger NHE3, which is largely responsible for intestinal and renal Na+ absorption, cycles between the plasma membrane and the endosomal recycling compartment under basal conditions, and its activity is regulated by changes in trafficking. But NHE3 is anchored to the actin cytoskeleton through interactions with the actin-membrane-linking protein ezrin and with NHE regulatory factors (NHERFs), which also bind ezrin. So how is NHE3 trafficking regulated? Mark Donowitz and colleagues investigate this question on page 2434 by examining how lysophosphatidic acid (LPA; an inflammatory mediator that stimulates NHE3 activity) affects NHE3 mobility in kidney epithelial cells. Their results indicate that the transient increase in NHE3 mobility, which is induced by LPA, occurs in two separately controlled parts. First, LPA regulates NHE3 exocytotic trafficking to the BB and, second, it controls the attachment of NHE3 to the BB cytoskeleton by regulating the NHE3-NHERF2 interaction. PI3K-dependent signalling controls the first of these processes, note the authors, but PI3K-independent signalling controls the second – a result that provides an important new insight into NHE3 regulation.