FBXO31, also known as F-box protein 31, is a substrate recognition protein of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. It plays a crucial role in mediating the ubiquitination and subsequent degradation of target proteins through the ubiquitin-proteasome system. In pancreatic cancer, FBXO31 is upregulated and promotes cancer progression by targeting proteins like SIRT2 for degradation (PMID: 38216561). In endometrial cancer, FBXO31 acts as a tumor suppressor by regulating the ubiquitination of OGT (O-GlcNAc transferase), which affects cellular O-GlcNAcylation levels (PMID: 39894887). FBXO31 Is a reader of C-terminal amides, which ubiquitylates CTAPs for subsequent proteasomal degradation. A dominant de novo D334N mutation in FBXO31 alters FBXO31 substrate recognition and CTAP clearance, causing some important proteins to be degraded and clinical intellectual impairment or diplegic spastic cerebral (PMID: 39880951).