SLC27A4 (FATP4) is a dual-function long-chain fatty acid transporter and acyl-CoA synthetase that regulates cellular lipid metabolism. As a membrane transporter, SLC27A4 mediates long-chain and very-long-chain fatty acid uptake across cell membranes, functioning as the principal fatty acid transporter in small intestinal enterocytes 1. Its enzymatic activity catalyzes ATP-dependent formation of fatty acyl-CoA, preventing fatty acid efflux and promoting continued uptake 2. SLC27A4 localizes to multiple cellular compartments including the endoplasmic reticulum, mitochondria, and peroxisomes, where it participates in lipid droplet-to-mitochondria fatty acid trafficking during fasting 3. Beyond lipid transport, SLC27A4 regulates autophagy by stabilizing ATG4B protein and influences hepatocellular carcinoma progression by promoting selective mono-unsaturated fatty acid uptake, conferring ferroptosis resistance 4. Mutations in SLC27A4 are associated with ichthyosis-prematurity syndrome and neurological disorders 5. Clinical relevance emerges in nonalcoholic fatty liver disease (NAFLD), where hepatic SLC27A4 overexpression promotes steatosis and inflammation via PXR pathway activation 6, and in hepatocellular carcinoma, where SLC27A4 overexpression correlates with poor prognosis and therapeutic resistance 47.