Solute carrier family 27 (Fatty acid transport protein) (SLC27)

The Fatty acid transport protein (FATP) family, members of the solute carrier family 27 (SLC27A1–6), consists of transmembrane proteins that facilitate the uptake and metabolic activation of long-chain fatty acids [1, 5]. These proteins are unique for their dual functionality, possessing both transport capabilities and intrinsic very long-chain acyl-CoA synthetase activity, which allows for "vectorial acylation"—the simultaneous transport and esterification of fatty acids to trap them within the cell [2, 11]. FATPs are expressed in key metabolic tissues such as the heart, liver, and skeletal muscle, where they act as gatekeepers for lipid flux [3, 12]. Dysregulation of FATP-mediated lipid uptake is strongly linked to lipotoxicity, a process central to the development of insulin resistance, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes [4, 6, 8]. Consequently, they are regarded as significant therapeutic targets, with inhibitors like Lipofermata (targeting FATP2) being explored for the treatment of metabolic disorders [4, 5]. Safety concerns regarding their inhibition include potential defects in the skin barrier (related to FATP4) and disruptions in bile acid homeostasis (related to FATP5) [5, 8].

Other names

Fatty acid transport protein familyFATP familyVery long-chain acyl-CoA synthetase familySLC27A familyVLCAS

Small-molecule inhibition of transmembrane fatty acid transport and intrinsic acyl-CoA synthetase activity to reduce ectopic lipid accumulation and prevent lipotoxicity.