Lasalocid A targets mutated MYD88 in DLBCL.NF-κB activation in DLBCL can occur via the myddosome complex formed by MYD88, the B-cell receptor (BCR) pathway, and the MYD88, TLR9, and BCR (My-T-BCR) complex. The MYD88 L265P mutation drives constitutive activation of this pathway, promoting oncogenic is survival in lymphoma B cells. Although BCR pathway inhibitors like ibrutinib can block this pathway, lasalocid A specifically targets mutated MYD88. Acting as a “molecular glue,” lasalocid A binds MYD88 L265P to E3 ligase RNF5, leading to ubiquitination and proteasomal degradation of MYD88 and selectively removing survival signals in tumor B cells, and thus is an emerging specifically targeted therapeutic approach.