Together, these findings raise the intriguing possibility that elevated KSR1 expression may function as a tumor suppressive mechanism in cancers harboring constitutively active RAS or RAF mutations by driving RAS/MAPK signaling into a state of toxic hyperactivation, whereas in tumors lacking such mutations (e.g., HCC, ccRCC), increased KSR1 levels instead enhance oncogenic signaling and promote tumorigenesis. The gene discussed is RAF1; the disease is nonpapillary renal cell carcinoma.