Fluid flow is known to play a role in the development and remodelling of both blood and lymphatic vessels. But how is fluid flow sensed and transduced into a response? Here, Michael Simons and colleagues identify a role for syndecan 4 (SDC4) in regulating flow-induced remodelling of the lymphatic vasculature in mice (p. 4441). They first show that Sdc4/ mice exhibit lymphatic vessel remodelling defects during the late stages of embryonic development. Notably, the alignment of valve-forming lymphatic endothelial cells (LECs), and hence valve formation, is perturbed in these mutants. The authors note that these defects are similar to those seen in mice mutant for Pecam1, which encodes a known flow-sensing molecule, but that Sdc4/; Pecam1/ double knockouts exhibit a more severe phenotype, suggesting that SDC4 and PECAM1 act via distinct pathways. Following on from this, the researchers demonstrate that SDC4 acts by regulating the planar cell polarity protein VANGL2; SDC4 knockdown LECs express increased levels of VANGL2 in response to flow and fail to align under flow, whereas the reduction of VANGL2 levels in these cells restores flow-induced alignment. Together, these findings uncover new regulators of flow-mediated remodelling in the lymphatic vasculature.