Altogether, these data reveal the central role of the SLC15A4-TASL-IRF5 pathway for endosomal nucleic acid sensing by TLR7 and TLR9, and highlights the SLC15A4-TASL complex as as potential therapeutic target for autoimmune diseases associated with aberrant activation of these receptors, such as SLE. The gene discussed is SLC15A4; the disease is systemic lupus erythematosus.