Isoform 2 of Afadin

Afadin (AFDN) is a large adherens junction-associated protein that mediates cell-cell adhesion and cytoskeletal organization through interactions with actin filaments and junction components (UniProt: P55196-1). The protein is widely expressed across tissues and plays structural roles in maintaining epithelial and endothelial integrity, as well as in neuronal synapse formation and stability.

In the central nervous system, Afadin supports synaptic architecture and neuronal connectivity through its role in junction-associated scaffolding. It is implicated in processes relevant to neurodegeneration, particularly those involving loss of cellular adhesion and cytoskeletal dysfunction.

Afadin shows reduced abundance in Alzheimer's Disease brain tissue relative to age-matched controls (Chaparral AD proteomics). Across examined subcellular fractions, the protein exhibits downregulation with a mean log2 fold-change of −0.61 in post-mortem AD brain samples analyzed by tandem mass spectrometry. This reduction may reflect synaptic loss and disruption of junction-mediated structural integrity characteristic of AD pathology.