BTRC (beta-transducin repeat containing E3 ubiquitin protein ligase) is an F-box protein that functions as the substrate recognition component of SCF(BTRC), an E3 ubiquitin-protein ligase complex 123. BTRC recognizes phosphorylated target proteins and mediates their K48-linked ubiquitination and proteasomal degradation 45. Key substrates include NF-κB inhibitors (IκBα, IκBβ, IκBε), enabling NF-κB nuclear translocation and transcriptional activation 126; β-catenin, linking BTRC to Wnt pathway regulation 7; and cell cycle regulators like CDK4, controlling proliferation 8. BTRC also regulates circadian rhythms through PER1/PER2 degradation and controls mTORC1 signaling via DEPTOR ubiquitination 91011. Dysregulation of BTRC expression associates with cancer progression and chemotherapy resistance. Elevated BTRC activity promotes NF-κB-dependent survival signaling in colorectal cancer, while miR-224-mediated BTRC downregulation reduces β-catenin levels and metastatic potential 7. Conversely, SelK-mediated suppression of BTRC reduces CDK4 degradation and enhances glioblastoma proliferation, correlating with poor prognosis 8. These findings position BTRC as a critical node integrating multiple oncogenic pathways, with therapeutic potential for cancer treatment.