DENND5B and epilepsy: In conclusion, we report a complex neurodevelopmental condition featuring cognitive impairment, variable epilepsy, and brain abnormalities in association with heterozygous de novo loss-of-function variants in DENND5B. Biochemical studies confirmed that DENND5B variants result in a decreased protein levels, and the functional investigation of the variants demonstrated a significant impact on the intracellular lipid metabolism and vesicle transport.