Isoform 2 of ATP-citrate synthase

ATP-citrate synthase (ACLY) is a cytosolic enzyme that catalyzes the conversion of citrate and CoA to acetyl-CoA and oxaloacetate, a critical step linking carbohydrate metabolism to lipogenesis and protein acetylation (UniProt: P53396-2). The enzyme functions at the intersection of metabolic and epigenetic regulation, playing roles in fatty acid synthesis and histone acetylation across multiple tissues. ACLY is expressed broadly but shows particular importance in lipid-synthesizing tissues and the nervous system.

ACLY alterations have been implicated in neurodegenerative and metabolic disease contexts. No UniProt-curated disease annotations are directly listed for this entry, though the gene has broader relevance to metabolic homeostasis across tissues.

In Alzheimer's disease, ACLY shows an ambiguous direction of change across subcellular fractions in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is 0.2885 across the analyzed fractions, suggesting minimal overall abundance shift, though directional inconsistency between compartments may indicate altered subcellular localization or compartment-specific dysregulation rather than global protein level change in AD pathology.