A comprehensive functional and structural analysis led by Giulio Superti-Furga at CeMM uncovered how mutations in the citrate transporter SLC13A5 disrupt neuronal metabolism, causing a severe epileptic encephalopathy. Using deep mutational scanning of nearly 10,000 variants, the study elucidated the molecular mechanisms underlying transporter dysfunction associated with developmental epileptic encephalopathy (DEE). These findings provide critical insights into citrate’s neuromodulatory roles and establish a foundation for therapeutic development targeting this rare neurological disorder.