Neuraminidase 1–Cathepsin A lysosomal multienzyme complex interface (NEU1–CTSA interface)

The Neuraminidase 1–Cathepsin A (NEU1–CTSA) lysosomal multienzyme complex interface is a critical protein-protein interaction site required for the stability and catalytic function of the sialidase NEU1. In the lysosome, NEU1 must associate with the protective protein/cathepsin A (CTSA) to avoid rapid intralysosomal degradation and to achieve its active conformation (UniProt: Q99519, P34059). This complex, which often includes beta-galactosidase (GLB1), is responsible for the degradation of sialylated glycoconjugates. Genetic defects that disrupt this interface or the individual proteins lead to severe lysosomal storage disorders, specifically Sialidosis (NEU1 deficiency) and Galactosialidosis (combined NEU1 and GLB1 deficiency due to CTSA mutations) (PubMed: 24631287). Beyond its lysosomal role, the NEU1–CTSA complex translocates to the cell surface, where it regulates signaling by desialylating receptors such as EGFR, TLR4, and insulin receptors, linking it to cancer progression, inflammation, and metabolic diseases (PubMed: 21555519). Therapeutic strategies targeting this interface include pharmacological chaperones designed to stabilize the complex in patients with missense mutations, as well as small-molecule inhibitors aimed at blocking NEU1-mediated signaling in inflammatory contexts.

Other names

PPCA-NEU1 complex interfaceProtective protein/cathepsin A-neuraminidase 1 complex interfaceLMC interfaceLysosomal multienzyme complex interface

Stabilization of the multienzyme complex to restore enzymatic activity or inhibition of the NEU1 catalytic site to modulate cell signaling.