Gap junctions allow intracellular exchange by enabling the passage of small molecules less than 1.8 kDa in size, such as ions, small peptides, second messengers, and metabolites ^[1]. They are formed by the pairing of two hemichannels called connexons, said hemichannels are formed by hexameric assemblies of connexins (Cxs) that ultimately function to physically connect adjacent cells ^[2]. Cxs are named according to their molecular mass: in this way, a connexin (Cx) that has a molecular mass of 43 kDa is called Cx43 ^[3].

Cxs are structurally similar: they have 4 hydrophobic transmembrane domains (M1-M4), two extracellular loops, one cytoplasmic loop, and free cytosolic N- and C-termini. The extracellular loops work to connect to the Cxs of neighboring cells, while the N-terminal and the C-terminal have been associated with small molecule selectivity ^[4]. Most of the information known today about the molecular biology of Cxs has been derived from studies on Cx43. However, recently many gap junctions and hemichannels have been structurally characterized at high resolution using X-ray crystallography and cryo-EM, presenting insights into the shared structural similarities among Cxs ^[5].

Panx1, similar to its counterparts, has 4 transmembrane domains (M1-M4), cytosolic N- and C-termini, two extracellular loops and one intracellular loop. Until recently, Panx1 was thought to oligomerize as hexamers, but new cryo-EM structures have revealed the channels to be heptameric ^[6]. Panx1 can be activated by mechanical stretching, extracellular concentrations of K⁺, intracellular concentrations of Ca²⁺, opening of the P2X7 channel, tyrosine phosphorylation at the intracellular loop, or by membrane depolarization ^[5]. Some extracellular loops of Panx1 may exhibit glycosylation, which interestingly may be the reason for their lack of ability to form gap junctions, as demonstrated by glycosylation-deficient Panx channels. As for gating kinetics, a recent study demonstrated that the C-terminal tail acts as a gate, blocking the intracellular entry until its cleavage by caspase 3 or 7 opens the channel, suggesting a caspase-dependent gating mechanism ^[7].

In the 'CBX' binding site of pannexin-1, Arg75, Trp74 might form the hydrogen bond interactions ^[8].

ATP, released through Panx1 channels, induces via activation of purinergic receptors (P2X7) further Panx1 channel opening, thereby increasing Panx1 activation ^[9]. PQ1 Succinate is a gap junction enhancer. It acts by restoring GJIC and increasing connexin expression in breast cancer cell lines while not affecting normal mammary cells ^[10].