Leucine rich repeat transmembrane proteins (LRRMTs) are synaptic adhesion proteins able to influence synapse development and function. LRRTM4, one of the 4 members of this protein group, is able to induce presynaptic differentiation and plays a significant role in excitatory synapse development. LRRTM4 polymorphisms have been linked to multiple neuropsychiatric diseases, but the underlying mechanisms are currently unclear. Therefore, we aimed to better understand the role of this gene for brain function by combining a battery of behavioural assays with transcriptomic and metabolomic analysis using zebrafish, a small cyprinid fish species readily amenable for genetic manipulation, that displays a wide array of behaviours. In situ hybridization of adult zebrafish brains revealed strong brain region-specific expression of lrrtm4l1, one of the zebrafish orthologues of LRRTM4, especially in the dorsal telencephalon, a brain area known for its important role for emotional affective behaviour. Lrrtm4l1-/- zebrafish displayed heightened anxiety, while other behavioural domains such as aggression, locomotion or social behaviour were unaffected by the gene knockout. RNAseq analysis revealed over 100 differentially expressed genes and an enrichment of pathways related to neural connectivity and fatty acid metabolism. The brain metabolome of lrrtm4l1-/- zebrafish was also significantly different from wild-type counterparts with multiple up- and downregulated metabolites. In conclusion, this study suggests that lrrtm4l1 plays an important role for anxiety and regulates important processes of the brain transcriptome and metabolome. These findings may help to better understand the link between human LRRTM4 and neuropsychiatric disease.