The high prevalence of vitamin D deficiency in RTT patients (Motil et al., 2011; Sarajlija et al., 2013), and the known ability of vitamin D to inhibit the NF-κB pathway (Stio et al., 2007; Chen et al., 2013b; Lundqvist et al., 2014), which is upregulated in brains of hemizygous null (Mecp2-/y) male mice (Kishi et al., 2016), raises the intriguing questions of whether this simple, cost-effective dietary supplement might rescue the aberrant NF-κB pathway activation in these mice, and whether it can contribute to phenotypic improvement. This evidence concerns the gene NFKB1 and vitamin D deficiency.