Pml, also known as promyelocytic leukemia protein, is a key organizer of PML nuclear bodies, which are membrane-less organelles in the nucleus. 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 that influence processes such as senescence. Dysregulation of Pml expression is associated with diseases, especially cancer, highlighting its biological importance. Genetic models, such as KO/CKO mouse models, are valuable tools for studying Pml's functions [1,2,3,4,5,6,7,8].

In promyelocytic leukemia, the oncoprotein PML/RARα inhibits PML nuclear bodies assembly, leading to leukemogenesis. This indicates that normal Pml-mediated assembly of these bodies is crucial in preventing this form of leukemia [3]. Murine PML-null primary cells are resistant to TGF-β-induced apoptosis, suggesting that Pml is involved in the TGF-β-induced apoptosis pathway. Cytoplasmic Pml activates TGF-β signaling, while nuclear Pml is related to TGF-β-induced caspase 8 activation and apoptosis [4].

In conclusion, Pml is essential for maintaining cellular homeostasis through its role in PML nuclear body formation and regulation of various signaling pathways. Studies using KO/CKO mouse models have revealed its significance in diseases like promyelocytic leukemia and in the TGF-β-related apoptosis process. Understanding Pml's functions can potentially guide the development of therapies for related diseases.