Over the last three decades, motor domain in schizophrenia and related disorders has gained more scientific and clinical relevance, especially with regard to early detection of motor side effects of antipsychotic medication, early psychosis prediction, clinical outcome monitoring, and identification of new targets for non-invasive brain stimulation. In line with this development, the NIHM Research Domain Criteria (RDoC) initiative has recently introduced a sixth domain devoted to motor abnormalities in order to provide key insights into the relationship between specific motor system deficits and behavioral abnormalities. In recognition of this development, this symposium will present and discuss recent experimental work on neural mechanisms and putative clinical implications of motor system dysfunction in psychotic, affective and neurodevelopmental disorders. In addition, this symposium will bring clinicians and scientists together to appreciate the advantages and challenges of motor domain-based transnosologic research. By combining model-based approaches and empirical evidence, this symposium aims to contribute to the further development of a dimensional and motor domain-based research agenda, which will lead to a better understanding of the psychotic, affective and neurodevelopmental disorders. We anticipate that the findings presented and discussed during this symposium will decisively stimulate further multimodal and prospective studies on motor dysfunction in mental disorders.