APPBP2 (amyloid beta precursor protein binding protein 2) functions as a substrate-recognition component of the CRL2(APPBP2) E3 ubiquitin ligase complex, which mediates protein degradation through the DesCEND (destruction via C-end degrons) pathway. The complex recognizes proteins bearing a C-terminal -Arg-Xaa-Xaa-Gly degron motif and targets them for ubiquitination and proteasomal degradation. Key substrates include truncated SELENOV selenoproteins and TSPYL2, a negative regulator of cell proliferation. CRL2(APPBP2)-mediated TSPYL2 degradation downregulates the aging marker P21waf1/cip1, thereby delaying mesenchymal stem cell senescence 1. In cancer pathology, APPBP2 expression is significantly elevated in non-small cell lung cancer (NSCLC) and correlates with enhanced proliferation, migration, and invasion. APPBP2 promotes NSCLC progression through PPM1D and SPOP regulation 2 and modulates gefitinib sensitivity via the miR-873-5p axis 3. In ovarian clear cell adenocarcinomas, 17q21-q24 chr17 gain resulting in APPBP2 overexpression negatively correlates with disease-free and overall survival 4. Similarly, APPBP2 amplification within the 17q23 region associates with aggressive breast cancer phenotypes 5. Additionally, APPBP2 may facilitate intracellular protein transport along microtubules. These findings establish APPBP2 as a potential therapeutic target and prognostic biomarker in multiple malignancies.