INTRODUCTION: The angiomotin family comprises of three scaffold proteins – Amot, Amotl1, and Amotl2 – that have been implicated in the regulation of cell polarity, migration, and proliferation. Recent in vitro studies have reported that Amot localizes to the synapses in mature neurons and regulates dendritic spine maturation. AIM(S): We have found that Amot, together with Yap1, the Hippo pathway transcription co‑activator, are critical for proper dendritic arborization and mice locomotor coordination. However, to date the function of the two other Angiomotins, Amotl1 and Amotl2, in neurons has not been investigated. METHOD(S): To study Amotl1 function in the mouse brain, we generated systemic and neuron-specific knock‑out (KO) mice. To assess general locomotion, we performed an open field test. Amotl1 KO mice sociability was evaluated with the three-chamber task, automatic Eco‑Hab approach, and nesting test. To record the animal’s anxiety response, we used the marble burying test. RESULTS: In the present study, we show that Amotl1 localizes to the synaptic compartments in neurons. Deletion of Amotl1 leads to hyperlocomotion, decreased anxiety-like behavior, and alteration in mice sociability. Amotl1 ablation causes an increase in volume of lateral ventricles in the mouse brain by 50%. These features have been previously observed in animal models of various psychiatric disorders, such as schizophrenia or autism. Interestingly, mass spectrometry analysis of neuron‑specific interactors demonstrated that Amotl1 binds to FMR1 and FXR1, mutations of which cause Fragile X syndrome. CONCLUSIONS: We identified a novel synaptic protein, Amotl1, the deletion of which causes behavioral deficits and that it could be a potential molecular target for the development of new therapeutics for neurological disorders. FINANCIAL SUPPORT: This research was supported by National Science Center (NCN) grants: UMO- ‑2018/29/B/NZ3/02675, UMO-2018/29/N/NZ3/02682.