Fumarate hydratase (FH) is a crucial enzyme encoded by the FH gene located on chromosome 1q42.3-q43, and it exists as a homotetramer. This enzyme catalyzes the reversible conversion of fumarate to L-malate in the tricarboxylic acid (TCA) cycle, playing a key role in cellular metabolism and energy production. FH has two forms: a mitochondrial form involved in the TCA cycle and a cytosolic form that participates in amino acid metabolism and DNA damage repair. Germline mutations in the FH gene are associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a syndrome characterized by an increased risk of developing leiomyomas in the skin and uterus, as well as an aggressive form of renal cancer. The loss of FH function leads to the accumulation of fumarate, which stabilizes HIF1伪 and promotes tumorigenesis through the upregulation of HIF-target genes.