We report on a patient with chronic C4d-positive antibody-mediated rejection, who was subjected to treatment with bortezomib. Despite initial treatment with CD20 antibody rituximab and intravenous immunoglobulin, the patient presented with a steady increase in serum creatinine and de novo proteinuria. In an effort to directly target alloantibody-producing plasma cells and to prevent ongoing antibody-mediated graft injury, we applied treatment with a single cycle of bortezomib combined with dexamethasone. Treatment was associated with a > 50% decrease in DSA levels and disappearance of capillary C4d staining as detected in a follow-up biopsy. However, there were still profound glomerulitis, an unchanged degree of transplant glomerulopathy and a persistent discrete infiltration of the interstitium by CD138+ plasma cells. The clinical course was unfavorable: despite some decrease in urinary protein excretion, a further deterioration of kidney allograft function was noted. In summary, this case suggests distinct antihumoral efficacy of bortezomib also in the context of chronic AMR. Nevertheless, a major observation was that treatment failed to prevent deterioration of graft function. We speculate that, despite modulation of (complement-activating) DSA, advanced irreversible tissue injury in this late stage of rejection may have precluded a relevant clinical response. Together with other case studies, our results may provide a valuable basis for prospective trials designed to evaluate the efficacy of bortezomib in the prevention and treatment of earlier stages of chronic AMR, e.g. based on the results of early (protocol) biopsies and/or early post-transplant antibody monitoring.