FRRS1L is an important modulator of glutamate signaling that regulates AMPA receptor trafficking and postsynaptic membrane neurotransmitter receptor levels. The protein functions as an auxiliary regulatory factor for AMPA receptors, promoting their maturation and surface expression in neurons. Loss-of-function variants lead to accumulation of immature AMPA receptors with incomplete glycosylation, resulting in cytoplasmic retention and reduced postsynaptic membrane localization 1. FRRS1L deficiency causes developmental and epileptic encephalopathy-37 (DEE37), characterized by early-onset seizures (typically 6–24 months), severe global developmental delay, choreoathetosis, and hyperkinetic movement disorders 2. Cerebellar dysfunction is prominent, with impaired Purkinje cell dendritic spine formation and electrophysiological defects 3. Seizures often progress from infantile spasms to Lennox-Gastaut syndrome and may feature continuous spikes-and-waves during sleep 4. Recent evidence suggests FRRS1L disruption impairs social memory recognition, indicating broader roles in neurodevelopmental function 5. Sulthiame has shown promise in seizure management in FRRS1L encephalopathy 6, though most patients experience drug-refractory epilepsy requiring multi-drug regimens.