| Cathepsin Z Protein | |
|---|---|
| Gene | [CTSZ](/genes/ctsz) |
| UniProt ID | [Q9UBR2](https://www.uniprot.org/uniprot/Q9UBR2) |
| PDB Structures | 1DEU, 1FV7, 4CSO |
| Molecular Weight | ~34.6 kDa |
| Subcellular Localization | Lysosomes, extracellular |
| Protein Family | Cathepsin family, cysteine protease |
Cathepsin Z Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Cathepsin Z (also known as cathepsin X) is a member of the cathepsin family of cysteine proteases[1]. The protein is synthesized as a preproenzyme with an N-terminal signal peptide, a propeptide, and a mature catalytic domain[2]. Unlike other cathepsins, cathepsin Z contains a unique C-terminal extension with an RGD motif that mediates cell adhesion through integrin binding[3]. The active site contains the catalytic triad Cys-His-Asn characteristic of papain-like cysteine proteases[4].
Cathepsin Z is expressed in various cell types in the nervous system, including neurons, astrocytes, and microglia[1:1]. The enzyme participates in extracellular matrix remodeling, cell migration, and immune responses. In neurons, cathepsin Z may contribute to axonal guidance and synaptic plasticity through its role in extracellular proteolysis[5]. The protein is also secreted and can function extracellularly, where it may participate in wound healing and immune surveillance[6].
Cathepsin Z is upregulated in AD brain and localizes to amyloid plaques and neurofibrillary tangles[7]. The enzyme contributes to amyloid-beta generation through its ability to process APP and may also degrade tau protein[8]. Cathepsin Z deficiency in mouse models reduces amyloid pathology and improves cognitive function, suggesting a pathogenic role in AD[9].
Cathepsin Z is involved in the processing of alpha-synuclein and may contribute to its aggregation and toxicity[10]. The enzyme is upregulated in PD brain and in models of dopaminergic degeneration. Cathepsin Z also participates in neuroinflammatory responses through its interactions with immune cells[11].
Cathepsin Z is upregulated in ALS spinal cord and participates in the inflammatory response that drives motor neuron degeneration[12]. The enzyme may also contribute to the cleavage of extracellular matrix proteins and promote the spread of pathology. Cathepsin Z represents a potential therapeutic target in ALS[13].