RNF14 is an E3 ubiquitin ligase that functions primarily in translation quality control and transcriptional regulation. In its canonical role, RNF14 is recruited to stalled ribosomes by the collision sensor GCN1 and catalyzes Lys-6-linked ubiquitination of translation factors including eEF1A and eRF1, targeting them for proteasomal degradation 1. RNF14 also ubiquitinates ribosomal proteins (RPL0, RPL1, RPL12, RPS13, RPS17) and resolves RNA-protein crosslinks induced by reactive aldehydes like formaldehyde through K6-linked ubiquitination, with VCP-dependent removal and proteasomal degradation 23. Additionally, RNF14 regulates translation under amino acid limitation by promoting ribosome fall-off during arginine depletion 4. Beyond translation quality control, RNF14 acts as a transcriptional regulator in Wnt signaling through interaction with TCF transcription factors 5 and serves as a coactivator for androgen-dependent transcription 6. Clinically, RNF14 exhibits oncogenic roles in tumorigenesis, with elevated expression associated with colorectal cancer progression through Wnt/β-catenin pathway activation 78.