K_V2.2 is a member of the voltage-gated K⁺ channel superfamily. Together with the closely related K_V2.1 protein they form the K_V2 subfamily also known as Shab.

As with all K_V channels, K_V2.2 possesses the signature structure of the voltage-dependent K⁺ channels: six membrane-spanning domains with intracellular N and C termini. The functional K_V channel is a tetramer that can either be a homotetramer or a heteromer of K_V2.2 and K_V2.1 subunits.

Both K_V2.2 and K_V2.1 channels are known as delayed rectifiers that is, channels that are activated by changes in membrane potential (depolarization) but inactivate very slowly. The current they form is known as I_K or I_DR. Accessory subunits such as KChaP and the electrically silent a subunits K_V8 and K_V9 can modulate biochemical and biophysical properties of K_V2.2. 

K_V2.2 is expressed in the brain and in peripheral tissues such as gastrointestinal and vascular smooth muscle. Physiologically, K_V2.2 has a role in maintaining membrane potential and in modulating electrical excitability in neurons. In smooth muscle cells, K_V2.2 is probably involved in maintaining the contractile capacity of the cells.

The pharmacology of the K_V2.2 channel is somewhat limited. The channel is blocked by the classical K⁺ channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP). More recently, the small peptide toxin Stromatoxin-1 has been found to be a potent and more specific inhibitor of the K_V2 subfamily.