NOC3L (NOC3 like DNA replication regulator) is a nucleolar protein involved in ribosomal RNA (rRNA) processing and maturation. As part of the evolutionarily conserved NOC protein family, NOC3L functions in rRNA biogenesis, with reduced expression leading to accumulation of unprocessed pre-rRNA and impaired protein synthesis 12. NOC3L exhibits context-dependent roles in cancer: increased expression promotes tumor growth in gastric cancer through enhanced cell proliferation, where risk alleles increase NOC3L expression via altered transcription factor binding 3, while reduced expression correlates with tumor-suppressive effects across diverse cancer types 12. NOC3L is also associated with metabolic regulation; a functional genetic variant (rs11187850) acts as an expression quantitative trait locus (eQTL) in pancreas and adipose tissue, correlating with longitudinal fasting plasma glucose deterioration in T2DM progression 4. Additionally, NOC3L is implicated in immunological responses, with decreased expression observed in acquired immunodeficiency complicated by viral myocarditis and osteoporosis 5. Genetic variants in NOC3L are associated with colorectal cancer susceptibility in Han populations 6. These findings establish NOC3L as a multifunctional regulator spanning ribosome biogenesis, metabolic homeostasis, and tumorigenesis.