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

As with all K_V channels, K_V2.1 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_V2.1 and K_V2.2 subunits.

Both K_V2.1 and K_V2.2 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_V2.1.²

K_V2.1 is widely expressed throughout the body including brain, lung, pancreas, skeletal muscle and pulmonary artery.² 

The main function of K_V2.1 is to maintain membrane potential and to modulate the electrical excitability in neurons and muscle. In rat pulmonary artery it probably mediates hypoxic pulmonary vasoconstriction together with the K_V9.3 subunit.³  

Several toxins from spider venoms are potent blockers (affecting the channels in the nanomolar range) of K_V2.1 channels. Among these the most potent and selective are Stromatoxin-1 (#STS-350), (12.7 nM)⁴ and Hanatoxin (42 nM).⁴