Endophilin-B1

Endophilin-B1 (SH3GLB1) is a 365-amino-acid protein with pleiotropic roles in membrane dynamics and cell death regulation (UniProt: Q9Y371). It regulates outer mitochondrial membrane dynamics, promotes membrane curvature-dependent protein recruitment, and facilitates membrane fusion. The protein orchestrates both caspase-dependent and caspase-independent apoptotic pathways by activating BAX/BAK1 and coordinates autophagy through association with the PI3KC3-C2 complex, regulating autophagosomes formation and endocytic trafficking (UniProt: Q9Y371).

Endophilin-B1 is widely expressed and functions in mitochondrial homeostasis and neuronal viability. Isoform 2 specifically supports neuronal cells by maintaining mitochondrial morphology and promoting cell survival, suggesting tissue-specific neuroprotective functions (UniProt: Q9Y371).

In Alzheimer's disease, Endophilin-B1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.45, Chaparral AD proteomics). This reduction may compromise mitochondrial integrity and autophagy capacity, processes critically affected in neurodegeneration, potentially exacerbating AD-associated pathology through impaired clearance of protein aggregates and dysfunctional mitochondria.