Hereditary cerebellar ataxias are a wide and heterogeneous group of neurological disorders characterized by motor incoordination, instability and developmental delay, with cerebellar neuron degeneration as a common hallmark. The genetic cause and the underlying pathophysiological mechanisms for many forms of ataxias are still unclear and, currently, there are no effective therapies. Recent studies have shown that loss-of-function mutations in the calmodulin-binding transcription activator 1 (CAMTA1), a calcium responsive transcription factor, are associated with childhood cerebellar ataxia and intellectual deficiency in humans. Zebrafish have been successfully used to model a range of neurological and behavioral abnormalities. In an attempt to establish a zebrafish model of hereditary cerebellar ataxia, we characterized the zebrafish CAMTA1 orthologue camta1a and its transcription pattern, and by making use of morpholino-mediated gene inactivation and the CRISPR/Cas9 genome editing tools, we analyzed the phenotype induced following zebrafish camta1a depletion. The amino acid sequence of camta1a display a 73% overall similarity with the human protein, and, like in mice and humans, expression analyses showed brain-enriched expression, with highest levels of transcript in the cerebellar granule cells and Purkinje cells. The injection of camta1a antisense morpholino oligonucleotides recapitulated salient features of ataxia. In particular, camta1a morphants presented abnormal movement pattern, with increased spontaneous contractions and shorter swimming path. Moreover, camta1a MO larvae showed a loss of Purkinje neurons. To confirm the phenotype obtained with camta1a knock-down experiments, we have generated camta1a genetic mutants by CRISPR/Cas9 genome editing, targeting the DNA binding domain of the protein. The analysis of camta1a homozygous mutant zebrafish (camta1a -/-) is under way, together with the identification and characterization of genes transcriptionally regulated by camta1a in the cerebellum. Our results so far validate zebrafish as a valuable model organism in which to investigate the molecular mechanism leading to the cerebellar neuron degeneration responsible for the ataxic phenotype in humans with CAMTA1 mutation.