FDFT1 (farnesyl-diphosphate farnesyltransferase 1) catalyzes the condensation of two farnesyl pyrophosphate molecules to form squalene, the first committed step of sterol biosynthesis 1. The enzyme operates through a two-step mechanism: formation of presqualene diphosphate intermediate followed by heterolysis, isomerization, and NADPH/NADH-dependent reduction [UniProt summary]. Beyond canonical cholesterol synthesis, FDFT1 plays unexpected roles in multiple cancers. In colorectal cancer, FDFT1 functions as a tumor suppressor, with downregulation correlating with malignant progression and poor prognosis 1. FDFT1 suppresses CRC proliferation by negatively regulating AKT/mTOR/HIF1α signaling 1. Conversely, in hepatocellular carcinoma and glioblastoma, elevated FDFT1 promotes malignancy through AKT pathway activation 2, 3. In breast cancer, FDFT1 inhibition by artemisitene induces apoptosis via the TNFR1/NF-κB/NEDD4 pathway 4. FDFT1 also regulates tissue-resident memory CD8+ T cell metabolism, with deletion promoting antitumor immunity 5. Clinically, FDFT1 dysfunction causes porokeratosis through germline and somatic alterations, responsive to statin therapy 6. FDFT1 expression is regulated by cholesterol levels and SREBP2, linking metabolic and transcriptional control 7, 3. Targeting FDFT1 represents a potential therapeutic strategy for multiple malignancies.