Disturbances to neuronal function at the level of the synapse are crucial features of neuropsychiatric disorders, such as schizophrenia. Synaptic dysfunction in the prefrontal cortex, and its consequences on neuronal circuitry and behaviour, have been extensively linked to the disease. In this study, we are characterising the functional and behavioural consequences of a recently discovered, schizophrenia-associated variant in the CACNG2 gene, coding for the postsynaptic protein stargazin (StgSCZ). The aim of our study is to uncover how dysfunction at the level of the synapse in the prefrontal cortex contributes to disease phenotypes.Previous in vitro characterisation showed that the StgSCZ variant has a damaging impact on protein function, leading us to generate a knock-in mouse model carrying this variant. Through an assay of behavioural tests, we have established that StgSCZ animals show impairments in cognitive function in a range of domains, including spatial memory and associative learning. We followed up with morphological and electrophysiological assays of prefrontal pyramidal neurons, showing alterations in dendritic spine morphology, as well as changes in neuronal excitability. Interestingly, we have also observed concurrent alterations in bioenergetic demands, with subtle alterations in mitochondrial function and morphology, as well as potential changes to mitochondrial Ca2+ dynamics. Taken together, our results so far indicate impairments to synaptic function at several levels in prefrontal circuitry. We propose that this knock-in model carrying a disease-associated variant of stargazin has significant construct validity for schizophrenia and provides a comprehensive basis for investigating disease mechanisms related to synaptic dysfunction involved in schizophrenia.