FATP4

FATP4, also known as fatty acid transport protein 4, is a member of the solute carrier family 27 (SLC27) and is encoded by the SLC27A4 gene in humans. It is involved in the uptake and metabolism of long-chain and very-long-chain fatty acids and possesses acyl-CoA synthetase activity, catalyzing the conversion of fatty acids to fatty acyl-CoA. This dual functionality supports intracellular trafficking and activation of fatty acids for lipid synthesis and energy production.

FATP4 is expressed in several tissues, with particularly high levels in skin, as well as in the intestine, placenta, and kidney. Subcellularly, it localizes to the plasma membrane and the endoplasmic reticulum, consistent with roles in fatty acid transport and activation and in lipid processing within cellular membranes. In the skin, FATP4 contributes to epidermal lipid metabolism and the formation of barrier lipids, including ceramides and other very long-chain fatty acids critical for stratum corneum integrity.

Clinical significance of FATP4 arises from mutations in SLC27A4, which cause ichthyosis prematurity syndrome (IPS). IPS is characterized by ichthyosis at birth, prematurity, and defects in skin barrier function, often accompanied by respiratory and other complications. Animal models with FATP4 deficiency demonstrate severe skin barrier defects and perinatal lethality, underscoring the protein’s essential role in epidermal lipid homeostasis.

In summary, FATP4 is a lipid transporter and activating enzyme essential for fatty acid metabolism, with a key role in skin barrier formation and human disease when disrupted.