Herpes simplex encephalitis is genetically heterogeneous, but so far, each variant has occurred in a gene encoding a protein involving either the innate immune sensor toll-like receptor 3 (TLR3), a regulator of its intracellular trafficking (UNC93B) or a component of the downstream signaling complex (TICAM1).11, 12, 13. The gene discussed is TLR3; the disease is herpes simplex encephalitis.