FASN (fatty acid synthase) is a lipogenic enzyme that catalyzes de novo fatty acid biosynthesis through a series of enzymatic activities including 3-oxoacyl-[acyl-carrier-protein] reductase and fatty acid synthase activity [GO Annotations]. Primary function: FASN catalyzes long-chain fatty acid synthesis, a process essential for both normal cellular metabolism and malignant transformation. Mechanism: FASN activity is regulated through multiple post-translational modifications and protein-protein interactions. The FBXW7β E3 ligase degrades FASN through ubiquitination, controlling lipogenesis in colorectal cancer 1. FASN undergoes palmitoylation, which affects protein stability and function; palmitoylation of mutant p53 by FASN enhances p53 accumulation and tumorigenic gain-of-function 2, while FASN-mediated palmitoylation of MHC-I promotes its lysosomal degradation 3. Nuclear neddylated PTEN dephosphorylates FASN, inhibiting its TRIM21-mediated degradation and promoting fatty acid synthesis 4. Disease relevance: FASN is prominently upregulated in multiple cancer types. In colorectal cancer, the EGF-CSN6-FASN axis drives tumor growth and poor prognosis 1. In hepatocellular carcinoma, FASN inhibition increases MHC-I levels, enhancing CD8+ T-cell cytotoxicity and synergizing with anti-PD-L1 immunotherapy 3. FASN upregulation in Clonorchis sinensis-related intrahepatic cholangiocarcinoma creates an immunosuppressive microenvironment and predicts poor immunotherapy response 5. In diffuse large B-cell lymphoma, ZDHHC21-mediated FASN palmitoylation decreases FASN stability, suppressing lymphoma growth 6. Clinical significance: FASN inhibitors (orlistat, TVB-2640) show therapeutic potential, particularly in combination strategies with immunotherapy or cetuximab 135, and with lanatoside C in DLBCL 6.