Most neurodegenerative diseases are associated with protein aggregation which in turn could be due to protein damage. One kind of protein damage results from the spontaneous isomerization of aspartyl and asparaginyl residues leading to structural alterations and potentially loss of function of the protein. A protein repair enzyme, namely Protein L-Isoaspartyl Methyltransferase (PIMT), specifically recognizes isoaspartyl residues and repairs them, restoring the original structure of damaged proteins. PIMT knock-out mice die at early stages due to fatal epileptic seizures. Better understanding the physiological role of PIMT may therefore enable us to modulate the progress of epilepsy. Due to limitations in using mouse models to investigate the molecular mechanisms involved in epilepsy, zebrafish (Danio rerio) emerges as a good alternative model organism to pursue this aim. There are two homologues of human PIMT in zebrafish: Pcmt and Pcmt-like. We found that both of them are ubiquitously expressed in many tissues, with the highest expression levels in the brain. We were able to show that both enzymes catalyse the same biochemical reaction as human PIMT. Both genes could successfully be knocked down using morpholino technology. Morphants showed a developmental delay and accumulated isoaspartyl-containing proteins. Preliminary results indicate that the morphants are prone to developing seizures and display disturbed calcium signalling, as observed in the transgenic zebrafish line GCaMP6. As calmodulin was previously found to be a major substrate of PIMT, our results suggest that PIMT is important to sustain normal brain activity, at least partially by supporting calmodulin-mediated calcium signalling.