EHD2

EHD2 is a member of the Eps15 homology (EH) domain-containing protein family that primarily regulates endocytic membrane trafficking and membrane protein recycling in mammalian cells^[1][2]. Mechanistically, EHD2 stabilizes caveolae at the plasma membrane and participates in actin cytoskeleton remodeling, linking membrane trafficking to cell shape and mechanotransduction^[1]. In disease models, dysregulation of EHD2 expression is associated with impaired endothelial function, altered adipocyte lipid uptake, and cardiovascular remodeling, suggesting its role in metabolic and cardiac pathophysiology^[1][3]. Compared with related isoforms such as EHD1 and EHD3, EHD2 exhibits a unique membrane association pattern and slower ATPase cycling, which confers isoform-specific regulation of caveolae dynamics^[1][2]. EHD2 has been targeted experimentally with engineered fusion proteins, such as IL2-EHD2-sc-TNF, to modulate regulatory T cell expansion, highlighting its potential for precise immunomodulatory applications^[4]. Small-molecule inhibitors that selectively target EHD family ATPase activity have been developed for related isoforms, providing a framework for future pharmacological intervention of EHD2-mediated pathways^[2]. Therefore, EHD2 functions as a crucial molecular link between membrane trafficking, cytoskeletal regulation, and disease-relevant cellular signaling, with distinct isoform-specific properties exploitable in experimental and therapeutic contexts^[1][2][4].

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