Gap junction delta-2 protein (GJD2)

Gap junction delta-2 protein (GJD2), also known as connexin-36 (Cx36), is a member of the connexin protein family that forms gap junction channels enabling direct cytoplasmic communication between neighboring cells[1][2][4]. GJD2 is predominantly expressed in neurons and pancreatic beta cells, where it is essential for synchronizing electrical activity, coupling neural oscillations, and coordinating the pulsatile release of insulin[2][5]. In the brain, Cx36 mediates fast electrical synapses between GABAergic interneurons and other neuron types, supporting synchronous activity underlying processes such as memory, attention, and vision[5]. Genome-wide association studies link genetic variation in the GJD2 region to myopia and other refractive errors, highlighting its function in ocular development and neuronal signaling[3]. Dysfunction or loss of GJD2/connexin-36 disrupts these networks, potentially leading to disorders of vision, glucose homeostasis, learning, memory, and possibly contributing to certain neurological diseases[3][5]. No selective drugs are approved to target Cx36 in the clinic, and current pharmacological interventions are largely non-specific experimental tools[4].

Other names

Connexin-36Cx36GJA9Gap junction alpha-9 proteinConnexin 36Gap junction protein, delta 2, 36kDa

(Experimental/Preclinical) Non-selective gap junction blockers (such as mefloquine or carbenoxolone) can inhibit Cx36-mediated electrical synapses by blocking the gap junction channel; no clinically selective agents are established[4][5].