Gap junction alpha-1 protein

Gap junction alpha-1 protein (GJA1) is the primary structural component of gap junctions, specialized intercellular channels that permit passage of small molecules and electrical signals between neighboring cells (UniProt: P17302). Beyond its canonical role in cell-to-cell communication, GJA1 participates in intercellular innate immune signaling by mediating translocation of second messengers such as 2',3'-cGAMP between virus-infected and neighboring cells, thereby amplifying antiviral immune responses (UniProt: P17302).

GJA1 is expressed broadly across tissues including heart, cochlea, and bladder, where it regulates potassium recycling, cardiac conduction, and bladder contractility respectively (UniProt: P17302). Genetic variants in GJA1 are associated with multiple developmental and systemic disorders including oculodentodigital dysplasia, syndactyly, hypoplastic left heart syndrome, and erythrokeratodermia variabilis et progressiva (UniProt: P17302).

GJA1 is upregulated in Alzheimer's disease brain tissue. Chaparral AD proteomics data from post-mortem AD brain versus age-matched controls show a mean log2 fold-change of +1.24 across 3 subcellular fractions (Chaparral AD proteomics). This elevation suggests a potential role in AD-associated neuroinflammatory or intercellular communication dysfunction, though the functional significance remains to be clarified.