NIFK (nucleolar protein interacting with the FHA domain of MKI67) is a nucleolar protein that functions as an RNA-binding protein 1 involved in cell proliferation and ribosomal biogenesis. NIFK interacts with Ki-67, the proliferation marker protein 1, and regulates cell cycle progression through multiple mechanisms. At the molecular level, NIFK promotes cancer progression via two primary pathways: (1) Ki-67-dependent cell proliferation 2, and (2) downregulation of casein kinase 1α (CK1α), which activates the oncogenic TCF4/β-catenin signaling pathway 2. In colorectal cancer specifically, NIFK silencing inhibits the MYC pathway, suppressing cell growth, metastasis, and fatty acid metabolism while promoting apoptosis 3. The lncRNA NIFK-AS1, functionally related to NIFK, operates through ceRNA networks including an NIFK-AS1/miR-637/AKT1 axis affecting HCC progression 4. Clinically, NIFK is significantly upregulated across multiple cancer types and correlates with poor prognosis 5. In hepatocellular carcinoma, high NIFK-AS1 expression predicts sorafenib resistance, while knockdown sensitizes cells to therapy 4. In colorectal cancer, NIFK expression negatively correlates with anti-tumor immune infiltration (CD8+ T cells, macrophages) 6, suggesting dual roles in both tumor cell proliferation and immune evasion. NIFK represents a pan-cancer biomarker with potential therapeutic significance 5.