2-hydroxyacyl-CoA lyase 2

2-hydroxyacyl-CoA lyase 2 (HACL2) is an endoplasmic reticulum enzyme that catalyzes C1-removal reactions in fatty acid alpha-oxidation via a thiamine pyrophosphate-dependent mechanism (UniProt: A1L0T0). The protein also participates in phytosphingosine degradation pathways, suggesting a role in lipid homeostasis.

HACL2 is primarily involved in cellular lipid metabolism within the endoplasmic reticulum. No baseline disease associations are documented in UniProt, though the protein's role in fatty acid catabolism positions it within metabolic networks relevant to neuronal energy homeostasis (UniProt: A1L0T0).

HACL2 is upregulated in Alzheimer's Disease brain tissue. Quantitative proteomics analysis of post-mortem AD brain versus age-matched controls demonstrated increased HACL2 abundance, with a mean log2 fold-change of 0.80 across subcellular fractions (Chaparral AD proteomics). This elevation may reflect compensatory or pathological changes in lipid catabolism associated with neurodegeneration.