KNOP1 (lysine-rich nucleolar protein 1) is a nucleolar protein with established roles in multiple disease contexts. Located on chromosome 16, KNOP1 localizes to the nucleolus and functions in protein and RNA binding 1. Mechanistically, KNOP1 interacts with NMNAT1 to regulate NAD+ homeostasis, which controls FoxO1 phosphorylation and nuclear retention, ultimately promoting GPX4 transcription—a key ferroptosis suppressor in breast cancer 2. This KNOP1/NMNAT1/FoxO1/GPX4 axis represents a critical node in ferroptosis regulation. Disease relevance spans multiple conditions. KNOP1 expression associates with Alzheimer's disease risk through immune cell-specific mechanisms, identified via Mendelian randomization across immune cell types 34. KNOP1 also shows associations with childhood body mass index as a candidate obesity gene 1 and shared genetic factors in gastrointestinal and neurodegenerative diseases 5. In cancer contexts, KNOP1 is significantly upregulated in breast and hepatocellular carcinoma tissues. High KNOP1 expression correlates with poor prognosis in both malignancies, enhanced tumor growth, and increased immune cell infiltration 26. KNOP1 also coexpresses with PALB2 in breast and pancreatic cancer 7. Clinically, KNOP1 emerges as a prognostic biomarker and potential therapeutic target for cancer and neurodegenerative disease management.