The human syncytiotrophoblast (hST) is a differentiated syncytial epithelium that covers the villous tree of the maternal-facing surface of the human placenta. The hST is covered by apical microvilli which are bathed by the maternal blood. This brush border epithelial membrane displays a number of transport properties including the ability to selectively transfer ions. Ion channels in hST allow the permeation of cations such as K and Ca, and anions such as Cl. 9 We recently identified the Ca-permeable, non-selective cation channel of hST as being a functional polycystin-2, the gene product of one of the ADPKD-causing genes, PKD2. Little is known, however, about the mechanisms that control and regulate ion channel activity, in particular polycystin-2, in this syncytial epithelium. The chorionic villous tree presents an intricate structure which is continuously growing by branching during gestation. This process requires a dynamic cytoskeleton. The hST apical membrane is supported by an intricate network of cytoskeletal structures. The apical cytoskeleton in hST encompasses a supramolecular structure known as the "syncytioskeletal layer" of a potentially supporting nature. Major cytoskeletal components including microtubules, 13 intermediate filaments, and actin-based networks 18 have been identified which may have distinct and interactive roles in the developing placenta. Apical hST microvilli have highly organized actin filaments, and apical hST membrane vesicles retain prominent microfilamental structures associated with the presence of structured actin. Thus, the microvillous actin cytoskele-