Fdft1, also known as Farnesyl-Diphosphate Farnesyltransferase 1, is a key gene in the cholesterol synthesis pathway, with Squalene synthase (SQS) encoded by it being a crucial regulator in this process [4,6]. Cholesterol synthesis is essential for cell membrane integrity, steroid hormone production, and bile acid synthesis, highlighting the overall biological importance of Fdft1. Genetic models are valuable for studying its functions.

In colorectal cancer, fasting upregulates Fdft1, which then inhibits aerobic glycolysis and proliferation by suppressing the AKT/mTOR/HIF1α pathway, indicating its role as a tumor suppressor [1]. In contrast, in tongue squamous cell carcinoma, Fdft1 acts as an oncogene, promoting oncogenesis, and its repression by piR-39980 can prevent oncogenesis through regulating proliferation and apoptosis via hypoxia [2]. In clear cell renal cell carcinoma, upregulated Fdft1 inhibits cell proliferation, migration, and invasion potentially via the AKT signaling pathway [3]. In glioblastoma stem cells, Fdft1 is transcriptionally regulated by SREBP2 and activates the AKT pathway to maintain stemness, and its inhibition can be a strategy to eliminate these cells [5].

In conclusion, Fdft1 is essential in cholesterol synthesis and plays diverse roles in different disease conditions. Studies using genetic models, such as potentially KO/CKO mouse models (not explicitly mentioned in all references but inferred as valuable), have revealed its significance in cancer-related biological processes like cell proliferation, migration, and stemness maintenance, providing insights into potential therapeutic strategies for cancers like colorectal, tongue squamous cell, clear cell renal cell carcinomas, and glioblastoma.