The TICAM1 gene encodes an important adaptor protein called Toll–IL-1 receptor (TIR) domain-containing adaptor molecule-1 (TICAM1). TICAM1s are comprised of two domains proline-rich N- and C-terminal domains and a central TIR domain; each one plays an important role in signaling and is essential for interactions with other TIR domains. This protein is involved in native immunity against invading pathogens, it mediates NF-kappa-B and interferon-regulatory factor (IRF) activation, and induces apoptosis by interacting with TLR3 and TLR4 through TICAM2. Defects in this protein are the cause of Herpes simplex encephalitis 4 (HSE4), a rare complication of human herpesvirus 1 (HHV-1) infection, characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes.