Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV-1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428). Activated by RNAs having enough uridines. Homodimer (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:29155428). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (By similarity). Interacts with BTK (PubMed:17932028). Interacts with SMPDL3B (By similarity). Endosomal localization confers distinctive proteolytic processing. Expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Ubiquitinated by RNF216; leading to degradation by the proteasome. Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins (PubMed:25297876). The cleavage is necessary for dimer formation and subsequent activation (PubMed:26929371). Belongs to the Toll-like receptor family.