Molecular Classification
Membrane scaffolding protein, Adaptor protein, Other
Other Names
Myc box-dependent-interacting protein 1, Amphiphysin-2, cBIN1 (for cardiac-specific isoform), Bridging Integrator-1
Disease Roles
Cardiovascular disease (notably heart failure with reduced or preserved ejection fraction)Skeletal myopathies including centronuclear myopathy and myotonic dystrophyNeurodegenerative disease (Alzheimer’s disease association)

Bridging integrator 1 Overview

Bridging integrator 1 is a membrane scaffolding/adaptor protein encoded by the BIN1 gene. The cardiac-specific isoform (“cardiac bridging integrator 1” or cBIN1) plays an essential role in organizing transverse tubule microdomains within cardiomyocytes that are critical for normal calcium handling during each heartbeat. Loss or reduction of cBIN1 disrupts these structures leading to impaired excitation-contraction coupling—a hallmark feature seen in various forms of heart failure. In addition to its structural role, BIN1 acts as a central signaling hub interacting with multiple proteins important for muscle cell function. Mutations or altered splicing can cause skeletal muscle diseases such as centronuclear myopathy and have been linked epidemiologically with Alzheimer’s disease. In cardiovascular medicine, decreased myocardial or circulating levels of cBIN1 correlate strongly with adverse ventricular remodeling and poor outcomes; thus it serves both as a promising biomarker (“cBINI score”) for diagnosis/prognosis—especially HFpEF—and an emerging therapeutic target via gene replacement strategies currently advancing toward clinical trials.

Mechanism of Action

Gene therapy to restore or augment cBIN1 expression aims to normalize t-tubule structure, improve calcium handling microdomains, reverse maladaptive remodeling, and rescue cardiac function in failing hearts by acting as a scaffold for key signaling proteins involved in excitation-contraction coupling

Biological Functions

Organization of transverse tubule (t-tubule) membrane microdomains in cardiomyocytes
Regulation of calcium handling and excitation-contraction coupling in heart muscle cells
Maintenance of cardiomyocyte structure and function
Synaptic vesicle endocytosis (in neural isoforms)

Disease Associations

Cardiovascular disease (notably heart failure with reduced or preserved ejection fraction)
Skeletal myopathies including centronuclear myopathy and myotonic dystrophy
Neurodegenerative disease (Alzheimer’s disease association)

Safety Considerations

  • As gene therapy is the main therapeutic approach under development, potential concerns include immune response to viral vectors such as AAV9, off-target effects, long-term safety/efficacy unknown at this stage. No major adverse effects reported so far in animal models but human data are pending.

Interacting Drugs

No approved drugs directly targeting BIN1/cBIN1 yet; gene therapy approaches using AAV9-cBIN1 are under preclinical/early clinical investigation for heart failure treatment

Associated Biomarkers

Biomarker
Plasma cBIN1 level (“cBIN1 score” or CS): a biomarker for diagnosis and monitoring of heart failure with preserved ejection fraction (HFpEF) and potentially other forms of cardiomyopathy. Lower plasma levels indicate greater risk/severity due to maladaptive remodeling.