A new review highlights the pivotal role of LSD1 (lysine-specific demethylase 1) in regulating critical cellular processes and its implications for human diseases. This article sheds light on how post-translational modifications (PTMs) influence LSD1 activity, impacting its function in gene regulation and disease progression.
LSD1 is a histone demethylase that plays a significant role in chromatin remodeling and gene expression by modifying histone H3 lysine residues. It interacts with various protein complexes, allowing it to serve as both a transcriptional activator and repressor. The intricate modifications of LSD1, including phosphorylation, acetylation, ubiquitination, methylation, SUMOylation, and S-nitrosylation, dictate its enzymatic activity, subcellular localization, and stability. The disruption of these modifications has been linked to multiple pathological conditions, including cancer, metabolic disorders, neurological diseases, cardiovascular conditions, and bone disorders.
The overexpression of LSD1 has been observed in various tumors, where it facilitates the suppression of tumor suppressor genes and promotes cancer cell proliferation. LSD1’s interaction with oncogenic pathways contributes to tumorigenesis and metastasis, making it a promising therapeutic target. In metabolic diseases, LSD1 has been implicated in adipose tissue differentiation and insulin sensitivity, suggesting potential strategies for obesity and diabetes management. Furthermore, LSD1 is crucial in neurodevelopment, with dysregulation linked to autism, Alzheimer’s disease, and amyotrophic lateral sclerosis.
The growing body of evidence on LSD1’s role in gene expression and disease mechanisms opens new avenues for targeted therapy. Inhibitors of LSD1 are currently being explored as potential treatments for cancer and neurological disorders, aiming to restore normal cellular function by modulating its activity. The findings presented in this review reinforce the significance of post-translational modifications as regulatory mechanisms and underscore the need for further research into precision medicine approaches targeting LSD1.
By expanding our understanding of LSD1 and its modifications, this research provides a foundation for developing novel therapeutic strategies, offering hope for improved treatments across a range of diseases linked to LSD1 dysfunction.

Funding Information:
Basic Research of Medical Science and Technique Foundation of Henan Province, China SBGJ202301004
Key Project of the High Education from the Education Department of Henan Province, China 22ZX008
Youth Supporting Program from Henan Province, China 2021HYTP060
Youth Supporting Program from Zhengzhou University JC202044046
Science and Technology Project of Henan Province, China 232102311179
National Natural Science Foundation of China U21A20416
National Natural Science Foundation of China 82020108030
National Natural Science Foundation of China 82103997
China Postdoctoral Science Foundation 2021M692950
China Postdoctoral Science Foundation 2021M702942
# # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 7.3
Impact Factor: 6.9

# # # # # #

More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available online in ScienceDirect (https://www.sciencedirect.com/journal/genes-and-diseases ).
Submissions to Genes & Disease may be made using Editorial Manager (https://www.editorialmanager.com/gendis/default.aspx ).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.com
X (formerly Twitter): @GenesNDiseases (https://x.com/GenesNDiseases )

# # # # # #
Reference
Yinrui Li, Bo Wang, Yichao Zheng, Huiqin Kang, Ang He, Lijuan Zhao, Ningjie Guo, Hongmin Liu, Adil Mardinoglu, M.A.A. Mamun, Ya Gao, Xiaobing Chen, The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis, Genes & Diseases, Volume 12, Issue 3, 2025, 101307, https://doi.org/10.1016/j.gendis.2024.101307