Abstract Schizophrenia is among the most disabling diseases of humankind, affecting 1% of the world's population (in Brazil, almost 2.5 million people are affected). One of the biggest hurdles faced by most patients is the poor efficacy of current antipsychotic medication. This stems from the lack of understanding of schizophrenia's pathobiology and the lack of biomarkers and biological mechanisms associated with a positive medication response. By employing state-of-the-art proteomics and lipidomics in blood plasma collected in vivo from patients before and after treatment, we aim to identify predictive biomarkers for medication response. These will be used to compose a mass spectrometry-based molecular assay to aid psychiatrists in predicting the likelihood of a successful treatment before initiating medication. This will be the first clinical test ever developed to determine medication response in psychiatry. Moreover, by analyzing the proteomes and lipidomes of these blood plasma samples, we can also better understand the biochemistry and biology involved the response. To develop new and more effective medication, we must increase our understanding of the molecular aspects of schizophrenia. Therefore, we will test several of the biological hypotheses our group has built over the past few years. For that, we are moving to a multidisciplinary approach employing CRISPR/Cas9, flow cytometry, proteomics, phosphoproteomics, lipidomics, interactomics, transcriptomics, and miRNA expression in coordination with several laboratories in Brazil and abroad to characterize postmortem brains and peripheral mononuclear blood cells from patients and mentally healthy controls. In addition, pre-clinical models will also be evaluated, such as induced pluripotent stem cell-derived neurons and glial cells, cerebral organoids, and cell lines of neurons, glia, and adipocytes. We will search for the validation of the key biological processes we found associated with schizophrenia such as tripartite synapses, spliceosomes, myelination, and energy pathway-associated alterations, as well as the role of the endocannabinoid system in glia. Results from these studies may point to biological processes that could be modulated by new drugs yet to be developed. Our results will lead to three major benefits in the field: 1) refining a biochemical assay able to predict the efficacy of medications currently available to patients, even before the treatment starts; 2) identifying key biochemical pathways associated with effective medication; 3) and better comprehension of schizophrenia's molecular basis and biochemistry, which is key for developing new treatments. Our project navigates from basic to applied science, towards the establishment of translational strategies driven by personalized and precision medicine concepts, helping to bring the bench closer to the bedside.