In summary, we have uncovered a mutation, GluN2BV618G, that selectively alters BK–NMDAR complex formation and functional coupling, an effect that may underlie at least some of its pathogenic effects on GRIN2B-related neurodevelopmental disorder patients and suggests mechanisms by which BK–NMDAR complexes may modulate synaptic transmission and neuronal function. Here, KNG1 is linked to neurodevelopmental disorder.