KMT5B, also known as lysine methyltransferase 5B or SUV4-20H1, is a lysine methyltransferase that plays a crucial role in histone modification, which is essential for regulating gene expression. This process is involved in numerous biological pathways, especially those related to nervous system development and function [1,3,6-9]. Genetic models, such as mouse models, are valuable tools for studying the function of KMT5B.

In Kmt5b homozygous knockout mice, they were smaller in size than wild-type littermates, suggesting relative macrocephaly as seen in human patients [1]. Kmt5b haploinsufficient mice also showed a skeletal muscle developmental deficit with reduced muscle mass and body weight, affecting neuromuscular strength and NMJ structure [2]. In vivo knockdown of Kmt5b in the mouse embryonic cerebral cortex led to decreased proliferation and accelerated migration of neural progenitor cells [3]. Heterozygous Kmt5b mice had deficits in neonatal reflexes, sociability, and changes in thermal pain sensing, with some outcomes differing by sex [4].

In conclusion, KMT5B is essential for normal development, particularly in the nervous system and skeletal muscle. Studies using KO mouse models have revealed its role in processes like neurogenesis, neuronal migration, and muscle development. These findings contribute to understanding KMT5B-related neurodevelopmental disorders, including global developmental delay, autism, and congenital anomalies [1,3-7,9,10].