The autism spectrum disorder (ASD)-associated 16p11.2 gene quinolinate phosphoribosyltransferase (QPRT) is essential for neuronal differentiation but not proliferation of SH-SY5Y neuroblastoma cells. QPRT is part of tryptophan metabolism and catabolizes quinolinic acid (QUIN), a NMDA-R agonist neurotoxic for glutamatergic cells. However, we can exclude a QUIN-driven neurotoxicity in the SH-SY5Y model. In primary human neural progenitor cells, chemical inhibition of QPRT using phthalic acid (PA) leads to premature differentiation and a shift from neurons to astrocytes. Here, we employed cerebral organoids (COs) derived from human embryonic stem cells (H9) to validate the role of QPRT in a more mature neuronal model giving rise to various cell types. COs were treated with PA from d3 onwards and monitored over time, allowing to identify the onset of PA-induced changes during differentiation of distinct cell types: COs were analyzed via bulk RNA sequencing (d5/d10/d17/d40/d80) and scRNA seq (d112). Additionally, COs were fixed for immunocytochemistry and morphological analysis (d40/d80/d112) and will be analyzed for electrophysiological activity. At the transcriptomic level we report inhibition of QPRT to result in altered cell type ratios, starting during early progenitor differentiation and culminating in an excitation-inhibition imbalance via an increase of GABAergic and decrease of glutamatergic neurons accompanied by a shift to astrocytes at the mature state. Further detailed pathway analysis combined with the ongoing morphological and electrophysiological characterization will allow us to dissect the QPRT-specific etiology of ASD in 16p11.2 deletion carriers with the aim to identify new targets for potential pharmacological therapies.