SETBP1 haploinsufficiency disorder (SETBP1-HD) is a rare human genetic disorder (currently only 131 known cases) that affects development —particularly neurodevelopment. Individuals carry a hemizygous deletion or LoF in the SETBP1 region, which results in insufficient production of SET binding protein 1. Typically, SET binding protein 1 alters histone methylation to regulate the expression of target genes. When SETBP1 expression is low, key developmental genes are underexpressed, leading to developmental delay phenotypes. Symptoms include childhood hypotonia, motor development delay, intellectual and learning disabilities, anxiety, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The aim of this study is to establish whether zebrafish represent a useful biomedical model for SETBP1-HD. Specifically, we deleted a single copy of SETBP1 via CRISPR transgenesis to investigate whether zebrafish SETBP1 hemizygosity induces the behavioral syndromes characteristic of human patients. Social and cognitive behaviours were assessed through larval behavioural assays; including thigmotaxis, startle response, and light dark response. A zebrafish model of SETBP1-HD will increase pathophysiological understanding of the disease and help to determine the molecular underpinnings of disease-linked variants, including Schinzel-Giedion syndrome and leukemia. Zebrafish represent a great model for high-throughput drug screening, which means that our transgenic SETBP1-HD lines may aid in the screening and development of potential SETBP1-HD therapies.