Protein 4.1

Protein 4.1 (EPB41) is a major structural component of the erythrocyte membrane skeleton that stabilizes spectrin-actin interactions and regulates membrane mechanical properties. Beyond its well-established role in red blood cells, it recruits DLG1 to membranes and participates in dynein-dynactin complex and NUMA1 recruitment during mitotic cell cortex organization (UniProt: P11171). EPB41 is associated with hereditary elliptocytosis, an autosomal dominant disorder affecting red cell morphology and causing variable hemolytic anemia (UniProt: P11171).

In the context of Alzheimer's Disease, EPB41 shows elevated expression in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). Analysis of TMT-labeled subcellular fractions identified a mean log2 fold-change of +0.605, indicating upregulation across the measured fraction. This increased abundance in AD brain tissue suggests a potential role in disease-associated pathological processes, though the functional significance of this elevation remains to be determined.