Myc box-dependent-interacting protein 1

BIN1 (Myc box-dependent-interacting protein 1) is a membrane-sculpting protein that regulates plasma membrane curvature and mediates T-tubule formation in muscle cells (UniProt: O00499). It functions as a negative regulator of endocytosis and modulates intracellular vesicle sorting, with specific roles in BACE1 trafficking and amyloid-beta production. BIN1 also possesses actin-bundling activity and may regulate MYC-dependent cell proliferation.

BIN1 is primarily associated with centronuclear myopathy (CNM2), a congenital muscle disorder characterized by progressive weakness and centrally located nuclei in muscle fibers (UniProt: O00499). Beyond muscle pathology, the protein's involvement in endocytosis and amyloid-beta regulation positions it within neuronal trafficking and proteostasis pathways.

In Alzheimer's Disease, BIN1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.46 across subcellular fractions in a TMT-labeled quantitative proteomics study (4 fractions: P2, P3, S2, S3). This reduction may impair membrane remodeling and endocytic capacity, potentially affecting both amyloid-beta clearance and tau aggregate internalization in affected neuronal circuits.