NOC4L (nucleolar complex associated 4 homolog) is a nucleolar protein essential for ribosomal biogenesis, particularly 40S ribosomal subunit synthesis and maturation of small-subunit rRNA 1. As the human ortholog of yeast Noc4p, NOC4L functions within the small-subunit processome and mediates nuclear export of ribosomal 40S subunits 1. Beyond its canonical ribosomal role, NOC4L exhibits unexpected cellular functions: it inhibits SIRT1-mediated p53 deacetylation, promoting p53 acetylation and cell apoptosis in a p53-dependent manner 1. In macrophages, NOC4L interacts with TLR4 to inhibit its endocytosis, thereby blocking the TRIF pathway and ameliorating low-grade systemic inflammation and insulin resistance 2. Clinically, NOC4L dysregulation associates with multiple diseases: colorectal cancer patients with high NOC4L expression show improved prognosis when TP53 is wild-type 1, while an ADAP1-NOC4L fusion transcript correlates with poor survival in metastatic colorectal cancer 3. NOC4L is also dysregulated in Alzheimer's disease entorhinal cortex and involved in ribosome biogenesis during KSHV lytic replication 45. Additionally, NOC4L participates in a nucleolar subcomplex containing EMG1 required for small ribosomal subunit synthesis 6.