Lysosomal protective protein (Cathepsin A) (CTSA)

Lysosomal protective protein, commonly referred to as Cathepsin A (CTSA), is a multifunctional enzyme essential for the structural integrity and catalytic activity of the lysosomal multienzyme complex (LMC). It primarily functions as a chaperone, forming a stable complex with beta-galactosidase and neuraminidase-1 (NEU1) to prevent their premature degradation by lysosomal proteases [UniProt: P10619]. In addition to its protective role, it exhibits serine carboxypeptidase activity at acidic pH and deamidase/esterase activities at neutral pH, participating in the inactivation of bioactive peptides such as endothelin-1, bradykinin, and substance P [NCBI Gene: 5476]. Genetic mutations in the CTSA gene result in galactosialidosis, a rare lysosomal storage disease characterized by the secondary deficiency of NEU1 and beta-galactosidase, leading to the accumulation of sialylated oligosaccharides and glycopeptides [OMIM: 256540]. Therapeutic development for this target focuses on enzyme replacement therapy (ERT) and gene therapy to restore the LMC and alleviate systemic and neurological symptoms [PubMed: 32824137]. As a therapeutic target, it is evaluated through the measurement of residual enzyme activity in leukocytes or fibroblasts and the monitoring of urinary sialyloligosaccharide levels [StatPearls: Lysosomal Storage Diseases].

Other names

Cathepsin AProtective protein for beta-galactosidasePPCACarboxypeptidase CSerine carboxypeptidase L

Restoration of lysosomal carboxypeptidase activity and stabilization of the lysosomal multienzyme complex to prevent degradation of associated enzymes.