The ASPA gene codes for the hydrolytic enzyme called aspartoacylase. This enzyme catalyzes the deacetylation of N-acetylaspartic acid (NAA) in the oligodendrocytes in the central nervous system (CNS) to produce L-aspartate and acetate. The acetyl groups of NAA are used for the synthesis of lipid, which in turn are incorporated into myelin. The deficiency or ineffectively of this enzyme interferes with the normal hydrolysis of NAA and, thus, the availability of the acetyl group required for synthesis of the lipid portion of myelin. This would lead to impaired normal myelination, spongy degeneration of the white matter of the brain, and abnormal accumulation of NAA in brain and its excessive excretion in urine. In addition, it has been proposed that excess NAA leads to osmotic dysregulation because it has been proposed that NAA acts as an organic osmolyte that removes excess water from neurons by acting as a molecular water pump. Mutations in the ASPA gene lead to all these effects which are also seen in Canavan disease.

The ASPA gene is located on the short arm of chromosome 17 at 17pter-p13 and spans approximately 29 kb of genomic DNA with a coding sequence consisting of six exons. The ASPA protein consists of 313 amino acids weighing approximately 36 KDa. The ASPA-coding sequence is highly conserved across species during evolution. ASPA is strongly expressed not only in the oligodendrocytes in the nervous tissue, but also in other tissues, such as kidney, but the only known substrate, NAA, is present predominantly in the nervous system. During early postnatal central nervous system (CNS) development, the ASPA gene expression in oligodendrocytes is increased along with increased production of its substrate (NAA) in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA can perform its normal function.

To date, more than 55 mutations have been identified in the ASPA gene leading to Canavan disease. The majority of patients with Canavan disease are from an Ashkenazi Jewish background with two founder mutations (E285A) and (Y231X). These two mutations together account for 98% of the mutant alleles in Ashkenazi Jewish Canavan patients, whereas they account only 3% in non-Jewish patients. However, mutations in the ASPA gene among non-Jewish patients are different and more diverse with the mutation (A305E) seen more frequently among non-Jewish patients of European descent.