Cilia are highly conserved organelles protruding from dendrites of certain sensory neurons in C. elegans and from the cell surfaces of various cell types in other species. Since cilia are implicated in essential cellular processes, defects of ciliary structure and function have been identified as the underlying causes of severe genetic disorders collectively called ciliopathies. We make use of the X-box promoter motif recognized by the RFX transcription factor DAF-19, the major regulator of ciliogenesis in C. elegans, to identify genes involved in human ciliopathies. Using a C. elegans derived X-box search, we have identified several hundred human genes with conserved X-box motifs. The identified X-box genes are candidate ciliary genes as is the case in C. elegans, Drosophila melanogaster and other species. Currently, we focus on genes associated with dyslexia, the most common reading disorder. In the promoter regions of human DYX1C1, DCDC2 and KIAA0319, three of the most replicated dyslexia candidate genes, we identified conserved X-box motifs. We demonstrate their functionality as well as ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulatory interplay between human RFX1, RFX2, RFX3 and their effect on the endogenous expression of DYX1C1 and DCDC2 in human retinal pigment epithelial (RPE-1) cells. Induction of ciliogenesis increases the expression of RFX TFs and dyslexia candidate genes. Endogenous DYX1C1 localizes to the base of the cilium while DCDC2 localizes along the entire ciliary axoneme. Finally, over-expression of human DCDC2 leads to ectopic branching of ciliated neurons in C. elegans. Our results demonstrate that the evolutionarily conserved X-box promoter motif can be used to identify ciliary candidate genes across species.