SLC27A6 is a fatty acid transporter and acyl-CoA ligase that mediates long-chain fatty acid (LCFA) import across the plasma membrane and catalyzes ATP-dependent formation of fatty acyl-CoA 1. The protein plays a pivotal role in regulating LCFA availability in tissues with high beta-oxidation rates, particularly the heart 1. In cardiac physiology, SLC27A6 is essential for normal cardiomyocyte maturation and function. SLC27A6 knockdown in induced pluripotent stem cell-derived cardiomyocytes results in immature transcriptional profiles, abnormal morphology, and impaired calcium handling and contractility 2. The protein is associated with left ventricular hypertrophy pathways; SLC27A6 knockdown in cardiomyocytes downregulates caveolin-3 (CAV3), which is linked to hypertrophic phenotypes 3. Beyond cardiac tissue, SLC27A6 has disease relevance in multiple malignancies. In castration-resistant prostate cancer, SLC27A6 overexpression supports enzalutamide resistance through metabolic reprogramming, with high expression associated with poor survival 4. In papillary thyroid cancer, elevated SLC27A6 correlates with advanced N stage and promotes proliferation via c-MYC regulation 5. SLC27A6 appears in transcriptomic signatures for cervical cancer progression 6 and oral squamous cell carcinoma development 7. Genetic variants in SLC27A6 influence fatty acid composition in livestock, with specific SNPs affecting polyunsaturated and saturated fatty acid content 89.