Our data showing neuronal hypoexcitability in the face of largely unchanged values for VGSC α subunit mRNA abundance (except for Scn3a, which may reflect the developmental delay observed in Scn1b null brains) and protein subcellular localization predict that the major mechanistic deficit in Scn1b null cerebellum, in addition to disrupted neuronal pathfinding and fasciculation, is reduced chaperoning of VGSC α subunit proteins to the plasma membrane in the absence of VGSC β1 subunits, resulting in reduced INa density and reduced excitability (36). The gene discussed is SCN3A; the disease is Global developmental delay.