Isoform 2 of Protein enabled homolog

Enabled homolog (ENAH) is an actin-binding protein that regulates cytoskeletal dynamics and cell motility through its interactions with actin filaments and related signaling complexes (UniProt: Q8N8S7-2). The protein is expressed broadly across tissues and functions in processes including cell migration, axonal growth, and membrane dynamics. ENAH is structurally related to the Drosophila Enabled protein and participates in Rho GTPase signaling pathways that coordinate actin polymerization.

ENAH isoform 2 shows increased abundance in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.34 (Chaparral AD proteomics). This upregulation was detected via quantitative proteomics in post-mortem AD brain across subcellular fractions using TMT-labeled, data-dependent acquisition mass spectrometry. The modest elevation suggests potential involvement in cytoskeletal remodeling or compensatory responses within degenerating AD neurons, though the functional significance of this change remains to be determined. Further investigation is needed to clarify whether ENAH upregulation reflects pathogenic processes or neuroprotective mechanisms in AD pathology.