YWHAE, also known as 14-3-3ε, is a gene located on chromosome 17p13.3, and its product belongs to the 14-3-3 protein family. As a molecular scaffold, it participates in multiple biological processes such as cell adhesion, cell cycle regulation, signal transduction, and malignant transformation, and is associated with pathways like MAPK, NF-κB, and PI3K [2].

A mouse knockout of Ywhae was phenotyped to study its loss-of-function impact. In humans, individuals with heterozygous loss-of-function YWHAE variants (including single-nucleotide variants and deletions) exhibit developmental delay, delayed speech, seizures, and brain malformations such as corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Ywhae-/-mice also show brain structural defects like thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus, paralleling human findings. This indicates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities [1].

In conclusion, YWHAE plays a crucial role in various biological processes, especially in normal brain development. The study of Ywhae knockout mouse models has significantly contributed to understanding its role in neurodevelopmental diseases, highlighting its importance in this disease area.