NOL6 (nucleolar protein 6) is a multifunctional protein with dual roles in ribosome biogenesis and cancer progression. Structurally, NOL6 functions as a component of the small subunit (SSU) processome, participating in small ribosomal subunit assembly within the nucleolus by facilitating pre-rRNA processing, modification, and cleavage 1. Beyond its canonical ribosomal function, NOL6 has emerged as a potent oncogene across multiple cancer types. NOL6 is significantly overexpressed in prostate 2, gastric 3, colorectal 41, endometrial 5, lung 6, and breast cancers 7. Mechanistically, NOL6 promotes cancer cell proliferation and inhibits apoptosis through multiple pathways: in colorectal cancer, lactylation-stabilized NOL6 recruits STAMBP to deubiquitinate YY1, enhancing c-Myc transcription and establishing a positive feedback loop 4; in endometrial cancer, NOL6 regulates TWIST1 expression 5; in gastric cancer, NOL6 modulates critical downstream signaling pathways 3. Clinically, elevated NOL6 expression correlates with advanced tumor stages and poor patient prognosis 4. Therapeutic targeting of NOL6—through microRNA inhibition, lactylation site targeting, or small molecule inhibitors—has shown promise in suppressing tumor proliferation and metastasis in preclinical models 24.