FBXL18 (F-box and leucine-rich repeat protein 18) is a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes 1 that regulates protein stability through ubiquitin-dependent proteasomal degradation. The protein functions as a multi-substrate E3 ligase with diverse cellular targets and mechanisms. FBXL18 mediates K63-linked ubiquitination of Akt to promote its activation in glioma cells 2, while catalyzing K11-type ubiquitination of BST2 to stabilize the protein and enhance NF-κB-driven inflammation during rabies virus infection 3. In endometrial carcinoma, FBXL18 promotes cancer progression by targeting the phosphatase DUSP16 for degradation, thereby activating JNK signaling 4. FBXL18 also targets the pro-apoptotic protein Fbxl7 for degradation, thereby suppressing apoptosis 1, and degrades phosphorylated LRRK2 to attenuate toxicity associated with Parkinson's disease-linked mutations 5. Additionally, FBXL18 contributes to XPB destabilization in a CDK7-dependent manner 6. Clinically, FBXL18 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma and endometrial carcinoma, with knockdown reducing tumor growth and radiosensitivity 7. FBXL18 represents a potential therapeutic target across multiple cancer types and neurodegenerative diseases.