Yongfang Zhou

Acute ischemic events, such as myocardial infarction and ischemic stroke, are significant contributors to global morbidity and mortality. These pathological conditions, characterized by abrupt interruption of blood flow to critical tissues, induce substantial metabolic changes within affected tissues to maintain cellular viability under conditions of energy deprivation. ACSLs (acyl‐coenzyme A synthetase long‐chain family members) are key regulators of this metabolic adaptation, as they catalyze the conversion of long‐chain fatty acids into acyl‐coenzyme A thioesters, thereby affecting lipid metabolism, energy production, and cellular signaling pathways. Growing evidence highlights the crucial role of ACSLs in the pathophysiology of ischemic events because of their tightly regulated cell‐ and tissue‐specific responses to hypoxia, oxidative stress, and inflammation. In this review article, we explore the current literature on the molecular mechanisms by which ACSLs influence metabolic pathways, energy homeostasis, and cell fate determination during ischemia. Additionally, we evaluate whether ACSLs are promising therapeutic targets for reducing ischemic injury and promoting neuronal recovery. By understanding the complex interactions between ACSL activity and ischemic pathophysiology, this review article aims to identify ACSL research gaps, highlight new research directions, and explore novel therapeutic interventions for cardiovascular and neurological disorders.