ETF1 (eukaryotic translation termination factor 1) is a core component of the eRF1-eRF3-GTP ternary complex that mediates translation termination in response to stop codons 1. ETF1 recognizes stop codons in the ribosomal A-site and catalyzes hydrolysis of peptidyl-tRNA, with eRF3 providing GTP-dependent cofactor activity 1. Beyond canonical termination, ETF1 functions in nonsense-mediated decay (NMD) as part of the SURF complex, which recruits quality control machinery to mRNAs containing premature stop codons 2. ETF1 also regulates programmed ribosomal frameshifting (-1PRF), essential for viral protein synthesis and cellular gene expression 3. Clinically, ETF1 is relevant to cystic fibrosis therapy: small molecule compounds like SRI-41315 suppress premature termination codons (PTCs) in CFTR by reducing eRF1 abundance, restoring protein function 4. Additionally, ETF1 ligands that modulate frameshifting without degrading the protein show promise as broad-spectrum antivirals against SARS-CoV-2 and other viruses 3. A KDM3B-ETF1 fusion gene has been identified in invasive ductal carcinoma, promoting metastasis through altered downstream signaling 5. ETF1 is located on chromosome 5, a region implicated in malignant myeloid diseases 6.