Canonical Wnt signalling is critically important in embryonic cell-type specification and cancer, while non-canonical Wnt signalling is primarily implicated in physical morphogenesis, especially planar cell polarity (PCP). Both are modulated by the polarity kinase PAR-1 (MARK2/3). PAR-1 phosphorylates the Wnt transducer Dishevelled, but there is evidence that it exerts control 25 through other targets. Here we describe an in vitro screen for new targets of PAR-1 in which we identified phosphatidyl-inositol-4-kinase-2-beta (PI4K2β) as a substrate. Perturbation phenotypes and reporter assays in vivo show that PI4K2β inhibits both canonical and noncanonical Wnt pathways, in contrast to PI4K2α, which promotes canonical but does not affect non-canonical signalling. We show that PI4K2β acts in Wnt-responding tissue, not in Wnt 30 production or secretion. Subcellularly, PI4K2β is cortically enriched, unlike PI4K2α, and is basolateral in polarised cells. Mutation of the PAR-1 phosphorylation site of PI4K2β mis-localises it and the endogenous core PCP protein, Vangl2. Our results reveal that PAR-1 interacts with the vertebrate PCP signalling pathway via PI4K2β. 35 signalling pathways including the canonical and non-canonical Wnt signalling pathways 3, 4, 5, 6 . However, regulation and cross-talk between PAR-1 and Wnt signalling components are not well understood. Both canonical and non-canonical Wnt pathways are initiated by binding extracellular Wnt protein, which acts through a Frizzled (Fz) receptor and Dishevelled (Dvl) to 45 activate downstream targets. Canonical Wnt pathway leads to stabilisation/translocation of βcatenin and transcriptional activation of target genes 7 , while non-canonical Wnt pathways diverge at the level of Dvl into the Planar Cell Polarity (PCP) pathway involving Rho/Rac small GTPase and Jun N-terminal kinase (JNK) or the Wnt/Ca 2+ pathway via protein kinase C (PKC) 8 . Functionally, the canonical pathway specifies dorsal structures during early Xenopus 50 development 9 , while the non-canonical pathways regulate cell polarity including that required for convergent extension movements during zebrafish and Xenopus gastrulation 10, 11 . The PCP pathway promotes polarisation in the plane of the epithelial cells, perpendicular to their apicobasal axis 12 , affecting cell morphology, at least in part independently of transcription 13 . A 55 key feature of this pathway is the asymmetric distribution of their core PCP components such as transmembrane proteins Frizzled (Fz) and Van Gogh (Vang) and cytoplasmic regulators Dishevelled (Dvl) and Prickle (Pk) both within and between cells 14 . Disruption of the core PCP proteins is associated with developmental abnormalities such as defects in convergent extension and neural tube closure 15, 16 and also implicated in cancer invasiveness 17 . Van Gogh-like (Vangl) 60 is a mammalian homologue of the Drosophila PCP gene Van Gogh (Vang) (also known as Strabismus). Vang/Vangl is known to be involved in the non-canonical PCP pathway via the activation of JNK 18 ....