Lysosomal protective protein

Lysosomal protective protein (CTSA, UniProt: P10619) is a 480-amino acid lysosomal enzyme that functions as a carboxypeptidase and protective cofactor essential for the stability and activity of beta-galactosidase and neuraminidase. It also possesses deamidase activity on tachykinins. Mutations in CTSA cause galactosialidosis (MIM 256540), a lysosomal storage disorder characterized by combined deficiency of these hydrolases, resulting in lysosomal dysfunction and progressive neurological deterioration across multiple phenotypic subtypes (UniProt: P10619).

CTSA is a lysosomal protein with documented roles in neurodegeneration through its association with lysosomal dysfunction. The disease manifestations of galactosialidosis highlight the importance of proper lysosomal enzyme function in preventing neurological decline, including myoclonus, ataxia, and cognitive impairment in juvenile/adult presentations.

CTSA is associated with Alzheimer's Disease and shows increased abundance in post-mortem AD brain tissue. According to Chaparral AD proteomics data from human post-mortem AD brain versus age-matched controls (TMT-labeled DDA proteomics across four subcellular fractions), CTSA is significantly upregulated with a mean log2 fold-change of 0.65. This elevation may reflect compensatory lysosomal responses to protein aggregation pathology characteristic of AD neurodegeneration.