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Cilia are evolutionarily conserved organelles that are essential for fertilization,respiratory clearance,cerebrospinal fluid circulation and establishment of organ laterality.Despite the recent progress in understanding cilia composition and assembly,the signaling cascade and mechanisms that regulate cilia formation and elongation are not understood.Here we report that the Leakytail(Lkt)/ABCC transporter is crucial to normal ciliogenesis through regulating prostaglandin E2(PGE2)efflux and signaling.Zebrafish lkt mutants display a reduction of cilia number and length,as well as cilia-associated phenotypes.The lkt locus encodes an ATP-binding cassette transporter(ABCC).We show that PGE2 is a physiological substrate of the Lkt/ABCC transporter,and that the lkt/abcc mutation abrogates PGE2 efflux due to mislocalization of the mutant protein to the cytoplasm.We demonstrate that the Lkt/ABCC-mediated PGE2 efflux regulates ciliogenesis through the G-protein-coupled EP4 receptor.Together,our findings delineate a novel ciliogenic signaling cascade(PGE2-Lkt/ABCC-EP4),define Lkt/ABCC-mediated PGE2 efflux as a regulatory step and also provide insights into the etiology of human ciliopathies.