Transmembrane emp24 domain-containing protein 10

TMED10 (transmembrane emp24 domain-containing protein 10) is a cargo receptor mediating protein vesicular trafficking and quality control between the endoplasmic reticulum and Golgi apparatus (UniProt: P49755). The protein functions as a component of COPI and COPII-coated vesicles, facilitating both anterograde and retrograde transport of secretory cargo, GPI-anchored proteins, and membrane receptors. It also serves as a primary receptor for ARF1-GDP on Golgi membranes and can oligomerize to form protein channels for leaderless cargo entry into the ER-Golgi intermediate compartment.

TMED10 is involved in trafficking of amyloid-beta A4 protein and soluble APP-beta release, and associates with the presenilin-dependent gamma-secretase complex to regulate gamma-cleavage of amyloid-beta (UniProt: P49755). The protein also mediates translocation and secretion of leaderless cytoplasmic proteins, including tau (MAPT) and galectins, processes enhanced by heat-shock chaperones.

In Alzheimer's Disease, TMED10 is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics; direction: up, mean log2FC = 0.93). This upregulation, observed across multiple subcellular fractions in TMT-labeled proteomics analysis, may reflect compensatory changes in protein trafficking and amyloid-beta processing pathways relevant to AD pathobiology.