K_ir5.1 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.

The family’s protein 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 heteromers.

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.¹

K_ir5.1 can co-assemble with other K_ir channels such as K_ir2.1, K_ir4.1 and K_ir4.2. In fact, heteromeric K_ir4.1/K_ir5.1 form the basolateral small-conductance K⁺ channel in distal nephron segments that is responsible for generating the basolateral membrane potential that determines the magnitude and direction of K⁺ diffusion from cell to peritubular fluid in the nephron.²

The K_ir5.1 homomeric channel was largely thought to be non-functional, although recent evidence demonstrates that K_ir5.1 homomers can form functional channels when co-expressed with the anchor protein PSD-95 in the brain where it is abundantly expressed.³