Schizophrenia is a multi-factorial disorder involving synaptic dysfunction. Although many genes have been identified as risk factors, few specific susceptibility genes for schizophrenia have been definitively implicated by analysis of copy number variations (CNVs). During a re-analysis of CNV data from the International Schizophrenia Consortium, and supported by genetic data from four other disease cohorts, Sanbing Shen and colleagues identified recurrent deletions of the serine/threonine kinase gene unc51-like kinase 4 (ULK4) in patients with schizophrenia and bipolar disorder, leading them to hypothesise that ULK4, about which little is known, is associated with mental disorders including schizophrenia. Here (p. 630), they report multiple cases of schizophrenia with CNV abnormalities specific to ULK4. The authors also sought to characterise some of the functional neurobiology of ULK4, first showing that it is highly expressed in the cortex and hippocampus. Knockdown of ULK4 compromised neuritogenesis and impaired branching of the neurites, and reduced cell motility in vitro. Silencing ULK4 also affected a number of signalling pathways that have been implicated in schizophrenia and neuronal function, including the ERK, p38, JNK and protein kinase C (PKC) pathways. Finally, the authors examined the functional consequences of Ulk4 deficiency in mice in vivo, and observed agenesis in the corpus callosum. These data identify ULK4 as a rare susceptibility gene for schizophrenia, and will hopefully contribute to a better understanding of the pathogenesis of this disease.

• © 2014. Published by The Company of Biologists Ltd