Isoform 1 of Long-chain-fatty-acid--CoA ligase 6

ACSL6 (long-chain-fatty-acid–CoA ligase 6) is an enzyme that activates long-chain fatty acids by catalyzing their conversion to acyl-CoA thioesters, a critical step in fatty acid metabolism and lipid biosynthesis (UniProt: Q9UKU0-1). The protein is 722 amino acids long and plays roles in diverse cellular processes including energy metabolism and membrane dynamics. ACSL6 is broadly expressed across tissues and participates in lipid homeostasis pathways.

In Alzheimer's disease, ACSL6 shows decreased abundance in post-mortem AD brain tissue compared to age-matched controls based on quantitative proteomics analysis of subcellular fractions (Chaparral AD proteomics). The mean log2 fold-change is −0.3771, indicating modest downregulation. This finding was derived from TMT-labeled differential mass spectrometry across four subcellular fractions (P2, P3, S2, S3) of human brain tissue.

The downregulation of ACSL6 in AD brain may reflect disrupted lipid metabolism and reduced capacity for fatty acid activation, potentially contributing to altered membrane composition, mitochondrial dysfunction, or impaired energy metabolism observed in neurodegeneration. However, the functional consequence of this change in disease pathogenesis requires further investigation.