Renal involvement is frequent in myeloma, and associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. PACAP dramatically prevents kidney injury caused by myeloma light chains through suppression of proinflammatory cytokines, by inhibiting p38 MAPK and translocation of NFkB via both PAC¹ and VPAC¹ receptors. PACAP also suppresses myeloma cell growth by affecting the internal milieu of myeloma in the bone marrow. These data presented render PACAP worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and also as a new antitumor agent in multiple myeloma.