FBXW4 is a component of the SCF (Skp1-Cullin-F-box) ubiquitin ligase complex that targets proteins for ubiquitin-mediated degradation 1. The protein interacts with Skp1, Cullin1, RBX1, and COP9 signalosome components in an F-box domain-dependent manner, and can bind ubiquitinated proteins within cells 1. FBXW4 appears to function as a tumor suppressor, as it is frequently mutated, lost, or under-expressed in various human cancers 1. Expression levels correlate with patient survival in non-small cell lung cancer 1. In glioma, FBXW4 is downregulated compared to normal brain tissue, with lower expression associated with higher tumor grades and increased mortality risk 2. Conversely, in acute myeloid leukemia, high FBXW4 expression correlates with poor prognosis and shorter survival 3. FBXW4 is located within genomic regions associated with split-hand/foot malformation, where duplications affecting FBXW4 exons 6-9 have been identified in affected families 4. The gene also shows involvement in immune processes related to osteoporosis and has been implicated in opioid use disorder through genome-wide association studies 56.