PCLAF (PCNA clamp-associated factor) is a cell-cycle regulated protein that functions as a PCNA-binding regulator of DNA repair and replication. During normal DNA replication, PCLAF associates with PCNA; upon DNA damage, this interaction is disrupted, allowing monoubiquitinated PCNA to recruit translesion DNA polymerase eta (POLH) to facilitate bypass of replication-blocking lesions. Beyond DNA repair, PCLAF regulates centrosome number and cell cycle progression 1. In lung tissue, PCLAF drives alveolar cell plasticity through the PCLAF-DREAM complex, which transactivates CLIC4 and promotes AT2 to AT1 cell differentiation via TGF-β signaling activation 1. Genetic ablation of Pclaf impairs AT1 cell repopulation, leading to lung fibrosis 1. In regenerating lungs, Pclaf+ cells demonstrate elevated plasticity and contribute to alveolar epithelial cell restoration 2. Clinically, PCLAF is significantly overexpressed across multiple human cancers including nasopharyngeal carcinoma, hepatocellular carcinoma, neuroblastoma, glioblastoma, and endometrial cancer 3456. High PCLAF expression correlates with poor prognosis, increased proliferation, enhanced migration/invasion, and G1/S cell cycle acceleration via E2F1/PTTG1 and Wnt/β-catenin pathways 378. PCLAF overexpression is dysregulated by NF-κB signaling 3 and reduced DNA methylation, without gene amplification 4. These findings suggest PCLAF as a pan-cancer therapeutic target and prognostic biomarker.