CNS and somatic disease in MPS animal models have been shown to be driven, in part, by the GAG‐induced inflammatory response through the TLR4/MyD88 signaling pathways, resulting in increased secretion of TNF‐α from cells such as microglia and macrophage, along with NLRP3 inflammasome activation.15, 16, 17, 18, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51. Here, TLR4 is linked to mucopolysaccharidosis.