FBXW8 is an F-box protein component of the CUL7-RING ubiquitin ligase complex that mediates substrate recognition and ubiquitination for proteasomal degradation 1. The complex catalyzes polyubiquitination of diverse targets including cyclin D1 (phosphorylated by ERK1/2), IRS1 (via mTOR-dependent S6 kinase phosphorylation), MAP4K1/HPK1, GORASP1, YTHDF1, PPT1, and the PDCoV nucleocapsid protein 1234567. Notably, the CRL7-FBXW8 complex couples to neddylated CUL1-RBX1 catalytic modules rather than functioning as a conventional self-contained ligase 8. FBXW8 regulates Golgi morphogenesis, dendrite patterning, and glucose-sensing lipolysis through ATGL degradation 49. Functionally, FBXW8 loss causes pre- and postnatal growth retardation in mice with elevated IGFBP1/2 levels, reflecting its essential role in growth control 10. In cancer, FBXW8 suppresses hepatocellular carcinoma metastasis via PPT1 degradation and inhibits breast cancer progression by preventing NUMB degradation 611. FBXW8 also functions as an antiviral factor against PDCoV through NDP52-mediated autophagic degradation of the viral nucleocapsid protein 7.