KMT5B in Cancerous and Noncancerous Diseases: Clinical and Mechanical Considerations

KMT5B, also known as SUV4-20H1, is a lysine methyltransferase, catalyzing the generation of H4K20me2 through methylation at the histone H4K20 site, and is increasingly recognized as a pivotal driver of various tumor and non-tumor diseases. Under physiological conditions, KMT5B and its catalytic product, H4K20me2, regulate several essential cellular processes, including DNA replication site selection, G1/S phase transition, DNA double-strand break repair, and stem cell homeostasis in neural and muscle tissues. Furthermore, they support the development of the cytoskeleton, cilia, heart, and lungs. Beyond its catalytic activity, the non-catalytic functions of KMT5B also contribute to genomic stability. Conversely, KMT5B dysregulation is associated with diverse pathologies: deficiency is linked to glioblastoma, sarcoma, and neurodevelopmental disorders, whereas overexpression correlates with hepatocellular carcinoma and chronic myelogenous leukemia. This review summarizes the biological functions and pathological roles of KMT5B identified over the past decades, highlighting its potential as a therapeutic target for both cancer and non-cancer diseases.