NOC2L (NOC2 like nucleolar associated transcriptional repressor) functions as a transcriptional corepressor with dual roles in nuclear and nucleolar processes. Primarily, NOC2L inhibits histone acetyltransferase activity by preventing acetylation of core histones at p53/TP53-regulated promoters in an HDAC-independent manner, thereby repressing p53- and TP63-mediated transactivation of target genes like p21/CDKN1A [UniProt]. NOC2L also participates in conserved rRNA processing and ribosomal maturation pathways, linking its function to protein synthesis regulation 1. In disease contexts, NOC2L exhibits complex, context-dependent roles. Pancreatic cancer GWAS identified NOC2L as a susceptibility locus (rs13303010, 1p36.33), with expression quantitative trait locus analysis supporting its candidacy as a pancreatic cancer susceptibility gene 2. In ovarian cancer, NOC2L is upregulated following paclitaxel treatment and promotes chemoresistance by suppressing histone acetylation of NDUFA4 and other NDUF proteins, inducing metabolic shift toward aerobic glycolysis 3. In preeclampsia, NOC2L is downregulated; its restoration inhibits trophoblast ferroptosis through the p53/SLC7A11 pathway, improving pregnancy outcomes 4. Additionally, rare NOC2L variants associate with autism spectrum disorder risk 5. These findings position NOC2L as a therapeutic target in cancer and pregnancy-related pathologies, with clinical significance varying by disease type and expression context.