NRIP3 (nuclear receptor interacting protein 3) is a nuclear receptor-interacting protein with proteolytic activity that functions as a tumor suppressor and regulates cellular proliferation and differentiation. In colorectal cancer, NRIP3 inhibits cell proliferation, colony formation, and invasion while inducing G1/S cell-cycle arrest, primarily through suppression of PI3K-AKT signaling 1. NRIP3 promoter methylation occurs in 50.6% of colorectal cancer samples and correlates with poor differentiation, lymph node metastasis, and reduced 5-year survival, establishing it as an independent poor prognostic marker 1. In neuroblastoma, L3MBTL2-mediated epigenetic silencing of NRIP3 promotes MYCN-amplified cell proliferation, while NRIP3 de-repression suppresses proliferation and promotes differentiation 2. NRIP3 methylation functions as a synthetic lethal marker sensitizing colorectal cancer cells to combined PI3K and ATR/ATM inhibitors 1. NRIP3 has been identified as a coronary artery disease-associated gene with regulatory effects on vascular smooth muscle cell gene expression 3. Additionally, NRIP3 DNA methylation is altered in suicide victims, particularly in the hippocampus, insula, and amygdala, suggesting involvement in neuropsychiatric pathology 4. NRIP3 has been identified in a rare KMT2A fusion-associated B-cell acute lymphoblastic leukemia case 5.