CENPL (centromere protein L) is a kinetochore component involved in chromosome 1 and mitotic progression. As a constituent of the CENPA-CAD complex, CENPL participates in kinetochore assembly and CENPA incorporation at centromeres. Beyond its canonical mitotic functions, CENPL has emerged as a significant oncogenic factor across multiple cancer types. In breast cancer, CENPL promotes cell proliferation and migration while suppressing CD8+ T cell and NK cell infiltration, correlating with poor prognosis 1. CENPL functions in hepatocellular carcinoma (HCC) through the MEK1/2-ERK1/2 signaling pathway to accelerate cell proliferation, glycolysis, and cell cycle progression 2. Elevated CENPL expression independently predicts adverse survival outcomes in HCC, pancreatic adenocarcinoma, and lung adenocarcinoma 345. In breast cancer, CENPL contributes to chemotherapy resistance by enhancing homologous recombination DNA repair through the E2F8-CENPL pathway 6. Pan-cancer analysis reveals CENPL upregulation associates with increased myeloid-derived suppressor cell infiltration and decreased T-cell/NK infiltration, linking CENPL to immunosuppression 5. These findings establish CENPL as both a prognostic biomarker and potential therapeutic target in multiple malignancies.