Abstract Background and Aims Mutations in PKD1 or PKD2 lead to autosomal dominant polycystic kidney disease (PKD) by allowing urine flow-sensing primary cilia to activate tissue growth signals. However, the responsible cilia-associated factors and a strategy to block them and cure PKD are elusive. Cilia also specify organ laterality. In this process, flow-stimulated cilia activate the cytosolic protein Bicaudal-C (Bicc1) to curb the translation and/or the stability of specific target mRNAs. To identify candidate regulatory factors, we investigated if Bicc1 ribonucleoprotein particle (RNP) formation involves known proteins linked to cilia and cystic kidney diseases. Method To address this question, we here used AlphaFold structure modeling of protein complexes, combined with in vitro reconstitution assays and live imaging of Bicc1 RNP assembly. To begin to validate these interactions, we tested by genetic approaches if specific interacting factors also regulate Bicc1 targets in cells and mice. Results We found that multivalent interactions with structured domains of the ankyrin repeat and SAM domain containing (ANKS) 3 and their allosteric regulation by the related ANKS6 protein inhibit or restore Bicc1 access to target mRNAs, respectively. Concomitantly, ANKS3 alone increased the solubility and fluidity of Bicc1, whereas co-recruitment of ANKS6 had the opposite effect, liberating Bicc1 to self-polymerize and to induce phase-transitioning of target mRNAs in gel-like meshworks. Conclusion Perturbations in Bicc1-ANKS3-ANKS6 RNP dynamics and altered translation of Bicc1 target mRNAs emerge as likely culprits regulating cyst formation downstream of ciliary defects. ANKS6 can be sequestered in cilia by inversin, and mutations in these proteins provoke kidney cysts in nephronophthisis patients. Therefore, besides systematically profiling Bicc1 RNPs, future studies should test if ANKS6 mediates their dynamic regulation by flow-stimulated cilia.