ANGEL2 is a 2',3'-cyclic phosphatase that catalyzes hydrolysis of RNA molecules bearing 2',3'-cyclic phosphate groups at their 3' ends, converting them to linear 3'-phosphates 1. The enzyme is essential for tRNA recycling by removing 2',3'-cyclic phosphate groups from cleaved tRNAs, enabling the nucleotidyltransferase TRNT1 to reattach CCA tails required for aminoacylation and translation 1. ANGEL2 antagonizes pre-tRNA processing and XBP1 mRNA splicing during the unfolded protein response by limiting 2',3'-cyclic phosphate substrate availability 1. Beyond canonical RNA processing, ANGEL2 functions as a cancer-relevant RNA-binding protein regulating tumor suppressor translation. ANGEL2 directly interacts with translation initiation factor EIF4E, abrogating the repressor RBM38's ability to bind EIF4E and thereby enhancing wild-type TP53 translation 2. Loss of ANGEL2 decreases TP53 expression, promoting cancer cell growth and chemoresistance to doxorubicin and etoposide 2. An ANGEL2-derived seven-amino-acid peptide (Pep7) rescues TP53 expression and resensitizes cancer cells to doxorubicin, suggesting therapeutic potential 2. ANGEL2 methylation status correlates with cervical cancer prognosis, positioning it as a potential epigenetic biomarker 3.