Pml, also known as promyelocytic leukemia protein, is a key organizer of PML nuclear bodies, membrane-less organelles in the nucleus [1,2,3]. These bodies play a crucial role in cellular homeostasis, orchestrating post-translational modifications like stress-induced SUMOylation, and serving as hubs in multiple signaling pathways influencing processes such as senescence [1]. Pml is also involved in cytokine signaling, immune response, and inflammation [5]. Dysregulation of Pml expression is associated with diseases, especially cancer, highlighting its biological importance [1]. Genetic models, like KO/CKO mouse models, can be valuable for studying Pml's functions.

In promyelocytic leukemia, the oncoprotein PML/RARα inhibits PML nuclear bodies assembly and leads to leukemogenesis, revealing the role of Pml in cancer-related processes [3]. Murine PML-null primary cells are resistant to TGF-β-induced apoptosis, indicating Pml's significance in TGF-β signaling-related apoptosis [4].

In conclusion, Pml is essential for maintaining cellular homeostasis, regulating multiple signaling pathways, and is involved in disease processes, especially cancer. Studies using KO/CKO mouse models have significantly contributed to understanding its role in TGF-β-induced apoptosis and leukemogenesis, providing insights into potential therapeutic strategies for related diseases.