NPRL3 functions as a critical component of the GATOR1 complex, which serves as a negative regulator of the mTORC1 signaling pathway in response to amino acid availability 1. The GATOR1 complex, containing NPRL3, DEPDC5, and NPRL2, exhibits GTPase-activating protein (GAP) activity toward RagA and RagB GTPases, promoting their conversion to inactive GDP-bound forms during amino acid depletion 1. This mechanism leads to mTORC1 release from the lysosomal surface and subsequent pathway inhibition 1. NPRL3 is clinically significant in epilepsy, with pathogenic variants causing familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy, and other focal seizure disorders 23. The epilepsy phenotype typically involves focal seizures with frontal or temporal onset, often sleep-related and drug-resistant, with seizure onset averaging 4.4 years 2. Approximately 20% of cases show focal cortical dysplasia, and sudden unexpected death in epilepsy occurs in 10% of families 2. Most pathogenic variants are loss-of-function mutations, leading to mTORC1 hyperactivation and metabolic dysregulation 14. Beyond epilepsy, NPRL3 also plays a role in erythropoiesis through metabolic regulation 5.