Slc27a4, a member of the solute carrier family 27, is crucial for fatty acid synthesis and β -oxidation. It functions as a fatty acid transporter, facilitating the movement of fatty acids across the cell membrane, which is involved in lipid metabolism pathways, a process of great biological importance in maintaining cellular function [2,3].

In hepatocellular carcinoma (HCC), Slc27a4 is significantly overexpressed, especially in the fatty-acids-enriched microenvironment. It promotes the selective uptake of mono-unsaturated fatty acids (MUFAs), leading to increased levels of MUFA-containing phosphatidylcholine and phosphatidylethanolamine in HCC cells, thus conferring resistance to lipid peroxidation and ferroptosis. Silencing Slc27a4 enhances the sensitivity of HCC to sorafenib treatment both in vitro and in vivo [1].

In mice, hepatocyte-specific deletion of Slc27a4 ameliorates non-alcoholic fatty liver disease (NAFLD) by suppressing phosphatidylcholine-mediated PXR activation, while its overexpression in the liver exacerbates diet-induced liver steatosis, inflammation, and fibrosis [2].

In conclusion, Slc27a4 plays a vital role in lipid-related biological processes. Gene-knockout and conditional-knockout mouse models have revealed its significance in diseases like HCC and NAFLD. These models provide valuable insights into the role of Slc27a4, potentially guiding the development of new therapeutic strategies for these diseases.