GLS, encoding glutaminase, is an enzyme that converts glutamine into glutamate, playing a crucial role in glutamate homeostasis. This process is involved in various biological pathways, and balanced GLS activity is vital for normal physiological functions [1,5]. Glutamate, the product of GLS-catalyzed reaction, is the most abundant central nervous system neurotransmitter, highlighting the importance of GLS in neural function [5].

A de novo Ser482Cys gain-of-function variant in GLS leads to hyperactivity, causing glutamate excess, which results in profound developmental delay and infantile cataract [1]. In contrast, a homozygous copy number variant in GLS that leads to complete knockout of GLS expression causes autosomal recessive spastic ataxia and optic atrophy [5]. GLS has also been studied in the context of various cancers. In breast cancer, its expression may serve as a diagnostic biomarker and is related to tumor growth, metastasis, and the immune tumor microenvironment [2]. In prostate cancer, GLS is up-regulated, and its knockdown suppresses cell proliferation and promotes apoptosis [3]. Additionally, in the Chinese Han population, certain GLS gene polymorphisms are associated with reduced lung cancer susceptibility [4].

In conclusion, GLS is essential for maintaining glutamate homeostasis, which is crucial for normal neural function and overall physiological balance. Studies on GLS, including those using gene knockout models in the context of diseases like developmental disorders, neurodegenerative conditions, and various cancers, have provided insights into its role in disease pathogenesis. These findings may potentially contribute to the development of new therapeutic strategies for these diseases.