Abstract
ATP Citrate Lyase (ACLY) is a central enzyme bridging carbohydrate metabolism and lipid biosynthesis, crucial for various physiological processes and implicated in numerous pathologies. This review comprehensively describes ACLY, a pivotal enzyme at lipid biosynthesis and cellular metabolism interface. It serves as crucial role for several physiological functions, making it a highly valued topic for research. Starting with a description of the biochemistry and molecular biology of ACLY, elucidating its structural features, functions, and regulatory mechanisms, particularly in lipid synthesis and histone acetylation. Considering the pathophysiological aspect, the review also examines the relationship between ACLY dysregulation and associated diseases, explaining its contribution to pathological conditions mechanistically. An explanation of ACLY inhibitors is as follows: an overview of these inhibitors, an understanding of their mechanisms of action, and an analysis of their effectiveness and specificity. The following sections transition from preclinical studies, summarising key findings and knowledge into therapeutic potential, to clinical trials. The review offers updated information about ACLY research, integrating data from multiple sources to give an in-depth understanding. It concludes with the challenges and outlook facing the developing ACLY inhibitors, considering the strategies to overcome these challenges and the upcoming path in research and development in this promising field. This comprehensive examination not only encapsulates the knowledge at present but also aims to inspire and guide future inquiries into the complex realm of ACLY and its potential as a therapeutic target, ultimately improving patient outcomes and quality of life.