Two novel mutations in the GRIN2B gene reduce glutamate affinity by >1000-fold, reduce the receptors proton-sensitivity, and exert a dominant-negative effect over receptors in neurons.

A comprehensive platform is established for the evaluation of both current and future individuals afflicted with the UBA5-associated developmental and epileptic encephalopathy.

Laboratory-based methods are presented that produce filamentous tau aggregates with the same structures as those observed in neurodegenerative disease.

Two genetically distinct Stxbp1 haploinsufficiency mouse models exhibit seizures and impairments in cognitive, psychiatric, and motor functions, representing robust preclinical models of STXBP1 encephalopathy with both construct and face validity.

Building on previous work (Guarani et al., 2015), MICOS (mitochondrial contact site) assembly and cristae junction formation are shown to have a critical role in human health.

An inducedpluripotent stem cell (iPSC)-based model of KCNQ2-associated developmental epileptic encephalopathy suggests that disease is driven by dyshomeostaic neuronal mechanisms that are downstream of loss of M-current.

A single amino acid change in a neuronal ion channel called KCNQ2 blocks ion flow, prevents protein localization on axons, and results in severe epilepsy and slowed neurological development.

Two genetic mouse models for HCN1-linked developmental epileptic encephalopathy display distinct biophysical changes in HCN1 ion channel properties but similar worsening of seizures in response to antiepileptic drugs, thereby recapitulating key features of the human disease.

SNAP25 disease mutations within the synaptotagmin interface impair vesicle priming and cause uncontrolled spontaneous release due to enhanced SNARE:SNARE interactions, whereas a mutation within the SNARE-bundle increases the fusion energy barrier.