Our findings underscore the implications of FH mutation on the HLRCC tumor proteome, highlight the dependence of these tumors on the NRF2 antioxidant response pathway and includes the description and validation of multiple transcripts and 2SC-modified protein targets that provide novel insights into molecular mechanisms underlying HLRCC disease pathogenesis. The gene discussed is FH; the disease is hereditary leiomyomatosis and renal cell cancer.