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Solute carrier family 27 member 4 (FATP4) is a multifunctional protein that functions as both a fatty acid transporter and a very long-chain acyl-CoA synthetase (ACSVL4) [5, 10]. It is primarily localized to the endoplasmic reticulum and is highly expressed in the small intestine, skin, and brain, where it facilitates the uptake and metabolic activation of long-chain and very long-chain fatty acids through a process known as vectorial acylation [11, 17]. FATP4 is essential for the formation of the skin's permeability barrier; loss-of-function mutations in the SLC27A4 gene cause Ichthyosis Prematurity Syndrome (IPS), a rare genetic disorder characterized by premature birth, severe skin scaling, and respiratory complications [5, 19]. In addition to its role in rare diseases, FATP4 is increasingly recognized as a therapeutic target in oncology and metabolic medicine, as its overexpression promotes tumor growth and invasion in breast and liver cancers and contributes to obesity-related insulin resistance [2, 7, 14]. Experimental inhibitors like Griseofulvin and Triacsin C have been used in research to block its enzymatic activity and reduce fatty acid flux, although systemic inhibition poses challenges due to the protein's essential role in intestinal absorption and skin health [1, 15].
Inhibition of fatty acid uptake and long-chain acyl-CoA synthetase activity
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