BackgroundDYX1C1 (DNAAF4)andDCDC2are two of the most replicated dyslexia candidate genes in genetic studies. They both have demonstrated roles in neuronal migration, in cilia growth and function and they both are cytoskeletal interactors. In addition, they both have been characterized as ciliopathy genes. However, their exact molecular functions are still incompletely described. Based on these known roles, we asked whetherDYX1C1andDCDC2interact on the genetic and the protein level.ResultsHere, we report the physical protein-protein interaction of DYX1C1 and DCDC2 as well as their respective interactions with the centrosomal protein CPAP (CENPJ) on exogenous and endogenous levels in different cell models including brain organoids. In addition, we show a synergistic genetic interaction betweendyx1c1anddcdc2bin zebrafish exacerbating the ciliary phenotype. Finally, we show a mutual effect on transcriptional regulation amongDYX1C1andDCDC2in a cellular model.ConclusionsIn summary, we describe the physical and functional interaction between the two genesDYX1C1andDCDC2. These results contribute to the growing understanding of the molecular roles ofDYX1C1andDCDC2and set the stage for future functional studies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12860-023-00483-4.