We propose a new combination with a UPS inhibitor (ixazomib, Ixz, approved for multiple myeloma) [16,17] using the pan-cyclophilin inhibitor rencofilstat (RCF, non-immunosuppressive analog of cyclosporin A, previously known as CRV431 [18,19]) to increase apoptotic cell death in all types of PCa/CRPC/NEPC cells but with less effect on non-cancer cells. The gene discussed is HMBS; the disease is plasma cell myeloma.