DNASE2B (deoxyribonuclease 2 beta) is an acidic DNase that hydrolyzes DNA without requiring divalent cations 1. It participates in apoptotic DNA fragmentation and plays a critical role in nuclear DNA degradation during lens cell differentiation 2. Evolutionarily, DNASE2B represents the ancestral gene of the DNase2 family, conserved across 700 million years in synteny with the Uox gene, while its paralog DNase2 originated later in jawless fish 1. Clinically, DNASE2B has emerged as a prognostic biomarker across multiple malignancies. In prostate cancer, tumor cell-derived DNASE2B is significantly overexpressed and promotes disease progression by enhancing M2 macrophage infiltration through PSA secretion 3. In lung adenocarcinoma and non-small cell lung cancer, DNASE2B expression correlates with poor prognosis and has been identified as an m6A-associated differentially expressed gene with prognostic significance 4, 5. In papillary thyroid carcinoma, DNASE2B functions as a lysosome-associated gene affecting cell proliferation and invasion 6. Additionally, a DNASE2B SNP (rs3738573) predicts chemosensitivity to docetaxel in gastric cancer 7. Importantly, DNASE2B disruption in Xenopus produces lens defects mimicking human cataracts, including impaired vision and nuclei retention in lens fiber cells 2, supporting its essential role in ocular development.