Human genetics and studies in animal models indicate at least three distinct mechanisms of enhanced TLR7 signaling that may coordinate during SLE pathogenesis: (1) continuous engagement of TLR7 due to endosomal abundance of stimulating ligands [4,8], (2) hypersensitive TLR7 due to gain-of-function mutations in the TLR7 gene that lower the activation threshold of TLR7 [10], and (3) increased expression of TLR7 due to a higher number of functional copies of the TLR7 gene [11] or single-nucleotide polymorphisms (SNPs) that render TLR7 transcripts resistant to degradation [12]. This evidence concerns the gene TLR7 and systemic lupus erythematosus.