K_ir2.1 is a member of the family of inward rectifying K⁺ channels. The family includes 15 members that are structurally and functionally different from the voltage-dependent K⁺ channels.¹ 

The family’s topology consists of two transmembrane domains that flank a single and highly conserved pore region with intracellular N- and C-termini. As is the case for the voltage-dependent K⁺ channels the functional unit for the K_ir channels is composed of four subunits that can assemble as either homo- or heterotetramers.

K_ir channels are characterized by a K⁺ efflux that is limited by depolarizing membrane potentials thus making them essential for controlling resting membrane potential and K⁺ homeostasis.

K_ir2.1 is a member of the K_ir2.x subfamily that includes four members (K_ir2.1- K_ir2.4) that are characterized by strong inward rectification and high constitutive activity.

K_ir2.1 is expressed in a variety of tissues including the heart, brain, vascular smooth muscle cells and skeletal muscles.

In the heart, K_ir2.1 is a molecular component of the I_K1 current that is responsible for setting the resting membrane potential, preventing membrane hyperpolarization due to Na⁺ pump activity, influencing propagation velocity, altering the electrical space constant, and promoting late phase repolarization.² In fact, mutations in K_ir2.1 channels have been linked to a form of long QT syndrome (LQT7) known as Andersen's syndrome that is characterized by cardiac arrhythmias, periodic paralysis, and dysmorphic features.³