Syntaxin-5

Syntaxin-5 (STX5) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family member that mediates vesicular transport between the endoplasmic reticulum and Golgi apparatus (UniProt: Q13190). It functions in vesicle tethering and fusion at the cis-Golgi membrane, maintains Golgi structure, and facilitates both retrograde and intra-Golgi transport pathways. The protein is also involved in cytomegalovirus infection by participating in viral assembly compartment formation.

Mutations in STX5 cause congenital disorder of glycosylation type 2AA (CDG2AA), a severe autosomal recessive condition characterized by early lethality, liver disease, skeletal abnormalities, and protein glycosylation defects (UniProt: Q13190). This disease reflects the critical role of syntaxin-5 in maintaining proper secretory pathway function during development and cell differentiation.

In Alzheimer's Disease, syntaxin-5 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.38, indicating modest but directional reduction across the measured subcellular fractions in TMT-labeled quantitative proteomics analysis. Reduced syntaxin-5 expression may impair intracellular trafficking and glycoprotein processing, processes implicated in amyloid and tau pathology.