The strategy of targeting IRAK proteins has demonstrated a clear efficacy against non-Hodgkin’s lymphomas (NHLs), myelodysplastic syndrome (MDS), T-cell acute lymphoblastic leukemia (T-ALL), and melanoma in preclinical settings [64,65], while small-molecule IRAK1/4 inhibitors, R835 and PF-06650833, are currently in clinical development for use in autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This evidence concerns the gene IRAK1 and systemic lupus erythematosus.