Developmental and epileptic encephalopathies (DEE) are a spectrum of severe neurological disorders with poorly understood aetiologies, often involving metabolic dysfunctions. Biallelic recessive pathogenic variants in the Solute carrier family 13 member 5 gene (SLC13A5) gene cause a severe form of DEE, characterized by intractable neonatal seizures, developmental delay, and tooth hypoplasia. SLC13A5 encodes the sodium-dependent citrate transporter (NaCT) on the plasma membrane, expressed in brain and liver. Recent investigations highlighted the relevance of NaCT in citrate uptake, influencing cellular energy metabolism and stress in hepatic human cells. Citrate, a pivotal metabolite in lipid and cholesterol synthesis, as well as energy regulation, holds significance in neuronal metabolism and its implications in epilepsy and other pathologies. Despite the crucial connection between NaCT, citrate, and brain dysfunction, the pathogenic mechanisms remain unclear and inadequately explored.Animal models fail to recapitulate the severe clinical phenotypes observed in patients, underlying the specific role of SLC13A5 in the human brain. Using induced pluripotent stem cells (iPSCs) from SLC13A5-epilepsy patients and controls (obtained through collaboration with the Tess Foundation), we have developed cortical organoids. We used these organoids to investigate the impact of perturbed NaCT and citrate metabolism on key stages in corticogenesis, including neural progenitor proliferation, differentiation, and maturation.Understanding the cellular and molecular mechanisms underlying the pathogenesis of SLC13A5-driven epilepsy is crucial for identifying potential novel targets for therapeutical intervention.