The main finding of this work is that TLR9 and TLR4 activation increases the expression of pro-survival genes, provides resistance to both reversible and irreversible proteasome inhibitors, and, at the same time, reduces the expression of BCMA, a broadly expressed surface protein and a target for bispecific antibody therapy and CAR T cells in MM. This evidence concerns the gene TLR4 and Miyoshi myopathy.