This plasticity enables the activation of latent biological programs—such as those governing DNA repair, proliferation, and metabolism—while repressing plasma cell-associated transcriptional networks typically targeted by standard MM therapies (e.g., corticosteroids, IMIDs, proteasome inhibitors) and immunotherapies (e.g., BCMA-directed therapies). Here, TNFRSF17 is linked to Miyoshi myopathy.