FTCD (formimidoyltransferase cyclodeaminase) is a metabolic enzyme located on chromosome 21.3 that catalyzes a critical step linking histidine catabolism to folate metabolism 1. The enzyme contains two functional domains with homology to bacterial proteins, suggesting it arose through ancient gene fusion 1. FTCD is highly expressed in liver tissue and mediates the conversion of formimidoyltetrahydrofolate, thereby regulating cellular tetrahydrofolate pools 2. Clinically, FTCD deficiency is an autosomal recessive disorder affecting the glutamate formiminotransferase pathway 1. Additionally, FTCD functions as an autoantigen in type 2 autoimmune hepatitis, where anti-FTCD antibodies are diagnostic markers alongside anti-CYP2D6 antibodies 3. In cancer biology, FTCD plays dual roles: its expression inversely correlates with chemotherapy resistance, as depletion of the histidine degradation pathway—where FTCD functions as a rate-limiting enzyme—significantly reduces methotrexate sensitivity by preserving tetrahydrofolate pools in cancer cells 2. Conversely, FTCD acts as a tumor suppressor, with reduced expression in lenvatinib-resistant hepatocellular carcinoma that is restored upon cabozantinib treatment 4. Furthermore, FTCD serves as a prognostic biomarker in colorectal liver metastasis, with expression patterns predicting clinical outcomes 5. These findings suggest FTCD represents a therapeutic target for improving chemotherapy efficacy and managing drug-resistant malignancies.