NOL12 (nucleolar protein 12) is a multifunctional RNA-binding protein with primary roles in RNA metabolism and genome maintenance. In the nucleolus, NOL12 regulates pre-rRNA processing by controlling the separation of large and small ribosomal subunit precursors and modulating nucleolar levels of fibrillarin and nucleolin 12. NOL12 also localizes to nucleoplasmic foci and cytoplasmic P-bodies, where it associates with DNA repair proteins including TOPBP1 and DHX9 at sites of replication stress 2. Mechanistically, NOL12 loss impairs DNA damage recovery through ATR-Chk1-mediated apoptosis, while NOL12 repression triggers p53-dependent nucleolar stress and cellular senescence 21. In retinal cells, NOL12 protects against UV-induced apoptosis by suppressing ATR activation 3. Clinically, NOL12 is significantly overexpressed in hepatocellular carcinoma, correlating with poor prognosis, advanced stage, and metastasis 4. NOL12 expression serves as a biomarker for chr22 aging in human fibroblasts 1 and may contribute to cardiovascular pathology through circRNA regulatory axes 5. These findings establish NOL12 as essential for maintaining genome integrity, ribosomal biogenesis, and cellular stress responses.