Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized 
by the presence of nucleic acid- and protein-targeting autoantibodies and an 
aberrant type I IFN expression signature. Aicardi-Goutières syndrome (AGS) is an 
autosomal-recessive encephalopathy in children that is characterized by 
mutations in numerous nucleic acid repair enzymes and elevated IFN levels. 
Phenotypically, patients with AGS and SLE share many similarities. Ribonuclease 
H2 (RNase H2) is a nucleic acid repair enzyme that removes unwanted 
ribonucleotides from DNA. In this issue of the JCI, Günther and colleagues 
provide an in-depth investigation of the mechanisms underlying the link between 
defective removal of ribonucleotides in AGS and SLE, and these findings will 
likely serve as a strong springboard to provide novel therapeutic inroads.