The NMDA-type family of ionotropic glutamate receptors plays critical roles in neurons and glial cells functions, such as synaptic development, plasticity, neuronal survival. Recently, de novo variants of GRIN genes -encoding GluN subunits of the NMDA receptors- have been associated with neurodevelopmental disorders, defining GRIN-related disorders (GRD), a rare developmental encephalopathy with a clinical spectrum resulting from primary defects on glutamatergic neurotransmission. The genetic heterogeneity underlying GRD aetiology might be addressed using zebrafish larvae model. In this study we have generated and performed a deep phenotypic characterization of deleterious grin1a and/or grin1b zebrafish genes, paralogous to human GRIN1.Following CRISPR-Cas9 generation of the grin mutant larvae, no alterations on survival rate were detected, grin genes spatio-temporal expression pattern in the main larval stages was characterized and the behavioural phenotypes were investigated in paradigms established using pharmacological acute GRD models. Importantly, zebrafish grin mutants recapitulated GRD-like behavioral alterations, notably affecting the central, autonomic and sensory nervous systems (epilepsy, GI tract and visual impairment, respectively). Ongoing experiments include transcriptomic analysis towards the identification of different alterations in GRD models and, essentially, to unveil new potential therapeutic targets for GRD patients. In summary, our results showed that the comprehensive phenotyping of Zebra-GRIN models will allow to define GRD-like alterations. More importantly, the identified phenotypic readouts will be employed to screen the therapeutic efficacy of repurposed and EMA-approved candidate drugs, to provide personalized therapies for GRD patients.