FBXO31 is a substrate-recognition component of the SCF(FBXO31) E3 ubiquitin ligase complex with diverse cellular roles centered on protein quality control and cell cycle regulation. Functionally, FBXO31 recognizes C-terminal amidated proteins (CTAPs) formed during oxidative stress and directs their ubiquitination and proteasomal degradation 1. Beyond oxidative stress responses, FBXO31 mediates ubiquitination of multiple cell cycle regulators: it promotes cyclin-D1 and cyclin-A degradation during G1 arrest following DNA damage 23, degrades CDT1 during G2 to prevent re-replication 4, and ubiquitinates MDM2 to enhance p53-mediated DNA damage responses 5. FBXO31 also targets non-canonical substrates including SIRT2, OGT, and PARD6A, regulating metabolic pathways and cell polarity 67. Clinically, FBXO31 functions primarily as a tumor suppressor: it is frequently downregulated in multiple cancers and loss associates with poor prognosis 89. However, context-dependent oncogenic roles exist in pancreatic cancer where FBXO31 overexpression promotes progression 6. Disease associations include autosomal recessive intellectual developmental disorder and cerebral palsy, where FBXO31 mutations impair cyclin-D regulation and neuronal connectivity 101. Therapeutically, restoring FBXO31 expression or activity represents a potential cancer treatment strategy.