Desensitization therapies have been used with modest success in kidney transplantation. Some candidates, however, have such great breadth and depth of anti-HLA antibodies that they remain incompatible with potential donors. Bortezomib has been used without much success in desensitization regimens, but we hypothesized that its use during induction may be helpful in targeting antibody production by long-lived plasma cells. This report describes a high-risk positive crossmatch son-to-mother transplant that was performed after desensitization. The induction immunosuppression was supplemented with bortezomib. Pre- and post-transplant immunosuppression, antibody monitoring, biopsy data, and the clinical course are described in detail. Following transplant, the patient had excellent early graft function. Serial biopsies did not reveal acute antibody mediated rejection. Despite excellent graft function, the patient underwent withdrawal of care and died due to complications of calciphylaxis and deconditioning. This case details the first report of bortezomib used as part of induction therapy in solid organ transplant. Donor specific antibody production remained stable after transplant, with near complete abrogation of class I specificities. There were no bortezomib-related complications.