Inwardly rectifying K⁺ (K_ir) channels allow K⁺ to move more easily in, rather than out, of the cell. They have diverse physiological functions depending on their type and their location. There are seven K_ir channel subfamilies that can be classified into four functional groups.

K_ir2.1 belongs to the K_ir2.x subfamily. The primary structure of K_ir2.1 is comprised of two putative membrane-spanning domains (TM1 and TM2) linked by an extracellular pore-forming region (H5) and cytoplasmic amino and carboxy terminal domains. The H5 region serves as the “ion-selectivity filter” that is shared with other K⁺-selective ion channels with the signature sequence T-X-G-Y(F)-G.

Although initially thought to form only homomeric complexes, it is now known that K_ir2.1 can function as a heterotetramer with other K_ir2.x subunits both in vitro and in vivo. 

After synthesis in the endoplasmic reticulum, K_ir2.1 is transported to the Golgi apparatus for post-translational modification, and then transported to the cell surface. Sequences in the NH2-terminal region have been identified as responsible for Golgi export.

K_ir2.1 is expressed in skeletal and cardiac muscle and contributes to the establishment of highly negative resting potential and long-lasting action potential plateau in various cells including cardiac myocytes. Inward rectification of K_ir2.1 is caused by intracellular ions such as Mg²⁺ and polyamines.

Andersen syndrome is caused by dysfunction of K_ir2.1. Patients with Andersen syndrome exhibit cardiac arrhythmias reminiscent of long Q-T syndrome, periodic paralysis, and dysmorphic bone structure in the face and fingers.