To ask how, mechanistically, OSRC-2 cells induce cachexia, we introduced a promiscuous biotin ligase (BirA) fused to an endoplasmic reticulum targeting signal (ER) into OSRC-2 cells and, as a control, 786-O VHL−/− ccRCC cells; 786-O cells do not induce profound cachexia in mouse xenograft assays. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.