Employing CRISPR/Cas9 technology, we first validated efficient removal of the circRNA by genomic deletion of the intronic cassette of cZNF292/cZfp292 which we termed Exon1A in vitro observing specific deletion of cZfp292 in multiple clones. Similarly, systemic knockout mice were depleted of circular Zfp292 but did not express altered host gene levels. Importantly, phenotypical screening showed no influence of cZfp292 on postnatal vascular growth in the retina but revealed poor endothelial cell alignment within the thoracic aorta of cZfp292 mutant mice (Cell length/width: WT: 3.3±0.08 vs. KO: 2.43±0.05, p-value=0.0007). Mechanistically, we excluded a function as miRNA-sponge, translational template or transcriptional regulator. Instead, density gradient centrifugations discriminating between protein bound and free RNA showed that cZNF292 associated with proteins and proceeded to identify interacting proteins by RNA-pulldowns and mass spectrometry. Strikingly, the significant enriched protein Syndesmos (SDOS) known as interactor of the focal adhesion adapter protein Paxillin was previously shown to regulate primary cilia and to take part in cytoskeletal rearrangement by interaction with Syndecan-4. Of note, Sdc4­^-/- mice exhibit a similar poor flow alignment of the endothelium. We therefore verified the interaction between cZNF292 and SDOS in vitro by means of RNA-immunoprecipitations, revealing an interaction of SDOS with circular (Fold IgG: 6.57±1.8) but not linear ZNF292 (Fold IgG: 1.76±0.9). To address the functional overlap, we silenced cZNF292 and SDOS and observed a significant reduction of primary cilia and an altered endothelial morphology, accompanied by a more prone localisation of PXN in focal adhesions. To further understand the influence of cZNF292 on SDOS, we mapped the respective interaction sites. Of note, predicted SDOS binding sites clustered around the back-splice site and experimental exploration showed that the cZNF292/SDOS interaction is partly driven by the circRNA specific Exon1A (Ex4-oligo K_D: 548 nM vs. Ex4+Ex1A K_D: 288 nM). Vice versa, mutation of RNA-binding residues on SDOS abolished the interaction with cZNF292. Functionally, overexpression of this SDOS-binding mutant was sufficient to mimic the effects of cell alignment and PXN relocation upon cZNF292 silencing.