Clinical studies continuously unveil the increase risk of neurodevelopmental disorders in association with specific genetic variants. The impact of these mutations on the signal cascades leading to alterations of the brain functions, is frequently unclear. This is the case for the cdkl5 gene, encoding the Cyclin-Dependent-Kinase-Like-5 enzyme, whose mutations are linked to CDKL deficiency disorder (CDD). This is neurodevelopmental disease characterized by impairment of cognitive and motor skills. Here, we aim to elucidate the pathophysiological mechanisms associated with the lack of Cdkl5, employing the CRISPR-Cas9 technique to generate a zebrafish cdkl5-/- mutant line and characterizing the morphological, behavioral, and neurophysiological alterations associated.First, morphological analysis across the first four weeks revealed developmental delays in mutant fish, with reduced body length and diminished brain width and volume compared to controls. Despite a preserved organization of the muscular tissue confirmed by birefringence analysis, the mutant fish show, during a light-dark paradigm, a significantly reduced distance travelled in free swimming condition, in particular following the light-to-dark transition. Moreover, using rapid light flashes as epileptogenic stimulus, mutant fish showed fast-darting type of movement and increased number of turns compared to controls. Evaluating the visuo-motor integration function using an optomotor response paradigm, we found a reduced swimming bout power emerging at 12 dpf, accompanied by an increase in the relative number of bouts. Additionally, brain functional recordings at cellular resolution revealed a reduced direction-tuning encoding capability. In conclusion, we present here the characterization of a cdkl5 mutant line closely resembling most of the CDD features.