Insufficient production of DNase I (mutations occurring in DNase1 and DNase1L3 genes) or a decrease of its activity (DNase inhibitors or the generation of anti-DNase antibodies preventing the enzyme access to NETs) result in an inefficient degradation of free-circulating DNA and could determine the production of anti-nuclear autoantibodies (ANA) associated with SLE and LN being both a biomarker and a pathogenic factor contributing to the development of this condition [22,44]. Here, DNASE1L3 is linked to lobular neoplasia.