On the other hand, substrate accumulation may also trigger an anomalous activation of other routes, such as the activation of a Toll-like receptor 4 (TLR-4) by Globotrialosil ceramide (Gb3) in Fabry disease (FD), which determines the response of the innate immune system [14] and endothelial disfunction [15]. The gene discussed is TLR4; the disease is Fabry disease.