ELOVL5 is a human gene whose product eLOVL5 (Elongation of Very Long Chain Fatty Acids 5) is an endoplasmic reticulum membrane-bound enzyme that catalyzes the rate-limiting step in the elongation of polyunsaturated fatty acids (PUFAs). ELOVL5 specifically elongates C18-C22 fatty acids, playing a crucial role in the biosynthesis of long-chain omega-3 and omega-6 fatty acids including docosahexaenoic acid (DHA) and arachidonic acid (AA) [1]. Variants in ELOVL5 have been implicated in Spinocerebellar Ataxia 38 (SCA38), Neurodegenerative Disease Risk, Metabolic Dysfunction. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
ELOVL5 (Elongation of Very Long Chain Fatty Acids 5) is an endoplasmic reticulum membrane-bound enzyme that catalyzes the rate-limiting step in the elongation of polyunsaturated fatty acids (PUFAs). ELOVL5 specifically elongates C18-C22 fatty acids, playing a crucial role in the biosynthesis of long-chain omega-3 and omega-6 fatty acids including docosahexaenoic acid (DHA) and arachidonic acid (AA) [1].
The enzyme is particularly important in the brain, where DHA and other very-long-chain fatty acids are essential components of neuronal membranes and myelin. ELOVL5-mediated fatty acid elongation supports:
Membrane fluidity and function
Synaptic vesicle dynamics
Myelin maintenance
Resolution of neuroinflammation via specialized pro-resolving mediators [2]
Disease Associations
Spinocerebellar Ataxia 38 (SCA38)
Heterozygous mutations in ELOVL5 cause autosomal dominant spinocerebellar ataxia type 38. Clinical features include:
Progressive gait ataxia with onset in adolescence or adulthood
Nystagmus and oculomotor abnormalities
Dysarthria
Cerebellar vermis atrophy on MRI
Associated macular degeneration in some patients [3]
The pathogenic mechanism involves impaired fatty acid elongation leading to altered membrane composition in [Purkinje cells](/cell-types/purkinje-cells) and photoreceptors.
Neurodegenerative Disease Risk
ELOVL5 polymorphisms have been associated with:
Age-related macular degeneration risk
Cognitive decline in aging populations
Altered omega-3 fatty acid profiles in neurodegenerative diseases [4]
Metabolic Dysfunction
Reduced ELOVL5 activity contributes to:
Aberrant lipid metabolism
Hepatic steatosis
Altered inflammatory responses
Expression
ELOVL5 is expressed in multiple tissues with brain-relevant localization: