NEMF (nuclear export mediator factor) is a key component of the ribosome quality control (RQC) complex that surveils translation and prevents accumulation of potentially toxic incomplete polypeptides 1. NEMF recognizes stalled 60S ribosomal subunits by binding nascent chain-conjugated tRNA and recruits the E3 ubiquitin ligase Listerin (LTN1) to mark incomplete proteins for proteasomal degradation 1. NEMF's primary catalytic function involves CAT (C-terminal alanine tailing): it recruits alanine-charged tRNAs to the ribosomal A-site and directs non-templated C-terminal alanine extension of stalled nascent chains 2. This poly-alanine modification serves dual purposes—exposing buried lysine residues for LTN1-dependent ubiquitination in the canonical pathway, and creating C-degrons recognized by alternative E3 ligases in Listerin-independent pathways 3. NEMF dysfunction underlies intellectual developmental disorder with speech delay and axonal peripheral neuropathy 4. Dysregulated NEMF activity contributes to neurodegeneration in Listerin mutations and may suppress toxic repeat-associated non-AUG translation in C9ALS/FTD and Fragile X-associated tremor/ataxia syndrome, suggesting therapeutic potential in repeat expansion disorders 4, 5. Additionally, NEMF coordinates with UFMylation machinery at the ER translocon to maintain protein synthesis fidelity 6.