TPD52L2 (Tumor protein D52-like 2) is a member of the TPD52 family that functions as an oncogenic regulator of cell proliferation and survival across multiple cancer types. The protein promotes cell proliferation and colony formation in breast cancer cells, with knockdown leading to G0/G1 cell cycle arrest and increased GSK3β phosphorylation 1. In gastric cancer, TPD52L2 accelerates cell proliferation, and its silencing causes cell cycle blockade in G0/G1 and sub-G1 phases while promoting apoptosis through PARP cleavage 2. The protein also enhances oxaliplatin resistance in gastric carcinoma cells, with knockdown inducing endoplasmic reticulum stress and apoptosis 3. In pancreatic adenocarcinoma, TPD52L2 is regulated by miR-217 and promotes cell proliferation, invasion, and migration through the PIK3CA/AKT signaling pathway 4. Notably, transcript variant 6 (V6) of TPD52L2 serves as a biomarker for basal-like breast cancer, correlating with pathological features and patient outcomes 5. In glioblastoma, TPD52L2 modulates cellular heterogeneity through Wnt/β-catenin/Snail signaling, affecting invasion, proliferation, and therapy sensitivity 6. Additionally, TPD52L2 participates in cellular stress responses as part of the HMGB1 interactome 7. Therapeutically, TPD52L2 fusion proteins (TPD52L2-ROS1) have been identified in inflammatory myofibroblastic tumors, responding to targeted therapy with crizotinib 8.