Consistent with this, the Nuclear Factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway, a key signaling cascade downstream of TLR4, has been shown to interact with mutant huntingtin protein exon 1 in mice.49 Moreover, a recent study reports that N171‐82Q HD mice lacking TLR4 have their lifespan significantly extended.50 The functional impact of the different TLR4 polymorphisms on glial cells and neurons, which seems to impact on motor function rather than cognition, is however not known. This evidence concerns the gene NFKB1 and Huntington disease.