ANGEL1 is a CCR4 deadenylase homolog that functions primarily in mRNA quality control, specifically in the non-stop mRNA decay (NSD) pathway 1. The protein exhibits weak RNA 2',3'-cyclic phosphatase activity, catalyzing hydrolysis of RNA molecules with 2',3'-cyclic phosphate groups at the 3' end to produce linear 3'-phosphate groups. ANGEL1 acts as a rate-limiting factor for NSD, which targets aberrant mRNAs lacking proper stop codons due to premature polyadenylation 1. The protein associates with mRNA coding regions and ribosome-associated quality control factors, monitoring translation elongation stalls through its conserved catalytic residue 1. ANGEL1 also functions as an eIF4E-interacting partner, localizing to the endoplasmic reticulum and Golgi apparatus where it partially co-localizes with eIF4E and eIF4G 2. Notably, ANGEL1 depletion stabilizes non-stop decay substrates but not nonsense-mediated decay targets, demonstrating pathway specificity 1. From a clinical perspective, an eIF4E-binding peptide derived from ANGEL1 induces rapid necrotic cell death in epithelial cancer cell lines through ATP depletion and F-actin network disruption, offering potential cancer therapeutic applications 3.