The identification of XIST as an endogenous sex-specific source of immunostimulatory TLR7 ligands unites 2 longstanding observations in SLE — the presence of the IFN signature and the disproportionate incidence in individuals with 2 or more X chromosomes (9, 20–22, 24, 37, 42, 43, 53). Here, TLR7 is linked to systemic lupus erythematosus.