In the SLE signaling pathway, we identified the dysregulation of several nodes involved in the (1) clearance mechanism (SSB, MACROH2A2, TRIM21, H2AX, and C1Q gene family), (2) autoantigen presentation by MHCII (HLA gene family, CD80, IL10, TNF, and CD86), and (3) end-organ damage (FCGR1A, ELANE, and FCGR2A). The gene discussed is TRIM21; the disease is systemic lupus erythematosus.