Endophilin-A1

Endophilin-A1 (SH3GL2) is a membrane-associated protein that plays a central role in synaptic vesicle endocytosis and regulates neurotrophin signaling. The protein may recognize and stabilize high-curvature membrane domains and is required for BDNF-dependent dendrite outgrowth, functioning in early endocytic trafficking downstream of BDNF-NTRK2 receptor activation (UniProt: Q99962).

The protein is expressed in neural tissue and operates within synaptic and endosomal signaling pathways critical for neuronal development and plasticity. No additional disease associations are documented in UniProt for this entry.

In Alzheimer's disease, Endophilin-A1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.84 (Chaparral AD proteomics). This upregulation was detected across TMT-labeled quantitative proteomics analysis of multiple subcellular fractions. The elevation in an endocytic protein may reflect compensatory responses to synaptic dysfunction or altered membrane trafficking dynamics characteristic of AD pathology.