Cathepsin A (CTSA)

Cathepsin A (CTSA), also known as lysosomal protective protein, is a multifunctional serine carboxypeptidase enzyme localized to the lysosome[1][2][5]. Its key roles include acting as a protease that degrades bioactive peptides (such as endothelin I, angiotensin I, bradykinin, substance P, and oxytocin) as well as serving a unique protective function. CTSA physically associates with and stabilizes beta-galactosidase and neuraminidase 1 within the lysosome, ensuring their enzymatic activity and protecting them from proteolytic degradation[2][3][5][7]. Mutations or deficiency in CTSA disrupt this multienzyme complex, causing the rare lysosomal storage disease galactosialidosis, which clinically manifests as combined beta-galactosidase and neuraminidase deficiency with systemic symptoms (e.g., cardiac, skeletal, and neurological features)[2][3][5][6]. Beyond lysosomes, CTSA modulates diverse bioactive peptides and has esterase and deamidase activities at neutral pH[5][7]. It is inhibited by specific nerve agents and organophosphates, and changes in its activity or genetic sequence serve as a diagnostic hallmark for certain inherited metabolic disorders[1][3].

Other names

Lysosomal protective proteinPPCAProtective protein/cathepsin ACarboxypeptidase CCarboxypeptidase LBeta-galactosidase protective proteinLysosomal carboxypeptidase AUrinary kininaseDeamidaseEsteraseGLB2GSLNGBEBeta-galactosidase 2Carboxypeptidase Y-like kininaseProtective protein for beta-galactosidasePPGB

Inhibition of catalytic activity (by irreversible covalent modification or small-molecule inhibition), Disruption of protein-protein complex formation, Potential modulation of lysosomal enzyme protection