EH domain-containing protein 3

EHD3 (EH domain-containing protein 3) is an ATP- and membrane-binding protein that regulates membrane reorganization and tubulation through ATP hydrolysis (UniProt: Q9NZN3). It functions as a key regulator of endocytic transport, controlling protein trafficking between early endosomes, recycling endosomes, and the Golgi apparatus. EHD3 also participates in dopamine receptor recycling and cardiac ion channel trafficking, and plays a specialized role in neuronal BACE1 sorting relevant to amyloid precursor protein processing.

EHD3 is broadly expressed across tissues and exhibits multiple roles in subcellular membrane dynamics. While UniProt reports no specific disease associations for this protein, recent proteomic studies indicate dysregulation in neurological contexts.

In Alzheimer's disease, EHD3 is significantly downregulated in post-mortem human brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.92 (Chaparral AD proteomics). This reduction may compromise endocytic trafficking capacity and BACE1 sorting efficiency in affected neurons, potentially contributing to altered amyloid processing in AD pathogenesis.