This gene encodes multiple isoforms of a membrane‑associated adaptor protein that can localize to the cytoplasm and, in some contexts, the nucleus. One isoform was originally identified as a MYC-interacting protein with characteristics of a tumor suppressor.^[6] BIN1 plays important roles in membrane curvature, endocytosis, and organization of specialized membrane structures such as transverse (T)‑tubules in striated muscle.^[8]

Isoforms expressed in the central nervous system participate in synaptic vesicle endocytosis and membrane trafficking through interactions with dynamin, endophilin, synaptojanin, and clathrin.^[9] Genetic variation at the BIN1 locus has been associated with risk of late‑onset Alzheimer's disease, and neuronal BIN1 isoforms interact with the microtubule‑associated protein tau.^[10][11]

Muscle-specific and ubiquitously expressed isoforms are essential for the formation and maintenance of T-tubules and excitation–contraction coupling in skeletal and cardiac muscle.^[7][8] Certain nuclear-localized isoforms have been reported to modulate cell cycle progression and to induce an apoptotic or growth‑suppressive response independent of caspase activation in tumor cells.^[12]

Studies in mice suggest that this gene plays an important role in cardiac muscle development and postnatal maturation of T-tubules.^[13] Alternative splicing of BIN1 generates numerous transcript variants encoding distinct isoforms with tissue‑specific expression patterns, and aberrant splice variants that attenuate BIN1 tumor-suppressor activity have been identified in several tumor cell lines and cancers.^[14][15]

In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear myopathy causing muscle weakness^[7] and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects.^[9] An association has also been found between BIN1 mutations and Alzheimer's disease.^[9] Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish,^[16] and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.^[17]