Table 3.

ACSL4 in diseases.

Type	Expression	Phenotype and Mechanism	Ref.
Obesity	Upregulation	Promotes the participation of arachidonic acid in phospholipids, leading to hepatic fat accumulation, inflammation in gonadal white adipose tissue, and insulin resistance	[112,113]
Cardiac remodeling and contraction	Upregulation	Short-term high-fat diet intake leads to downregulation of FUNDC1 and upregulation of ACSL4, which can result in lipid peroxidation-dependent defects in cardiac geometry and function.	[114]
Steroidogenesis	Normal	Promotes the formation of adrenal cholesterol esters and determines the fatty acyl composition of these esters	[115]
Vascular disease	Upregulation	Promotes the synthesis and metabolism of arachidonic acid and inhibits the secretion of prostaglandin E2 in vascular cells	[116]
Intestinal ischemia/reperfusion	Upregulation	Ischemia induces the upregulation of the SP1–ACSL4 cascade, promoting ferroptosis-dependent intestinal reperfusion injury	[33]
Myocardial ischemia/reperfusion	Upregulation	Promotes myocardial ischemia/reperfusion injury through lipid peroxidation-dependent ferroptosis	[117,118]
Pulmonary ischemia/reperfusion	Upregulation	Promotes pulmonary ischemia/reperfusion injury through lipid peroxidation-dependent ferroptosis	[119]
Cerebral ischemia/reperfusion	Upregulation	Promotes cerebral ischemia/reperfusion injury through the GPX4–ACSL4–ACSL3 pathway	[120]
Ischemic stroke	Upregulation	Thrombin-induced activation of serine protease induces ACSL4-dependent ferroptosis in neuronal cells, leading to ischemic stroke	[121]
Renal ischemia/reperfusion injury	Upregulation	Promotes renal damage and inflammation related to ferroptosis	[122]
Acute kidney injury	Upregulation	Promotes ferroptosis in renal tubular epithelial cells, leading to inflammation and acute kidney injury	[123,124,125,126]
Acute lung injury	Downregulation	Isoliquiritin apioside inhibits HIF1A, leading to downregulation of ACSL4 and preventing acute lung injury caused by intestinal ischemia/reperfusion	[127]
Non-alcoholic fatty liver disease	Upregulation	Induces the development of hepatic steatosis and fibrosis	[128,129]
Alzheimer’s disease	Upregulation	Induces ferroptosis-dependent brain damage and increases cytoplasmic phospholipase A2 in the mouse cortex	[130,131]
Parkinson’s disease	Upregulation	Induces ferroptosis in the substantia nigra brain pathway and mediates the production of cytokines	[35,132]
Multiple sclerosis	Upregulation	Induces ferroptosis-dependent encephalitis	[133]
Exertional heat stroke	Upregulation	Promotes muscle cell death induced by exertional heat stroke via ferroptosis	[134]
X-linked intellectual developmental disorder	Mutation	Induces X-linked intellectual developmental disorder	[24,135]