Work from our own lab has shown that TRIM21 differentially ubiquitinates different isoforms of IRF5, with IRF5-V1 and V-5 targeted or degradation by TRIM21 whereas IRF5-V2 and IRF5-V3 (IRF5-V2 linked to susceptibility to SLE) are resistant to TRIM21-mediated degradation, with obvious implications for downstream activity (158). Here, TRIM21 is linked to systemic lupus erythematosus.