Voltage-gated K⁺ (K_V) channels form functional entities by the assembly of four α subunits and auxiliary subunits. Various auxiliary subunits are known to interact with K_V channels thereby modulating various properties such as gating, activation and inactivation of the channels as well as influencing trafficking of the channels to the cell’s plasma membrane¹.

KChIPs (K_V channel interacting proteins) are cytoplasmic proteins which belong to the neural Ca²⁺ sensor (NCS) family of Ca²⁺ binding EF-hand proteins. To date, KChIP1-4 have been identified. All four KChIPs have a conserved C-terminal domain, which has four EF-hand-like Ca²⁺ binding motifs. The N-terminal region differs among the various KChIPs and attributes different properties regarding the regulation of K_V channels¹. KChIPs regulate different properties of K_V channels such as their cell surface expression (mediated by proper trafficking of the various subunits), channel assembly and gating^1-4. Specifically, KChIP2, 3 and 4 strongly regulate the activity of the K_V4 channel family in cortical pyramidal neurons⁵. Furthermore, KChIP knockout mice display an increase in anxiety-like behavior compared to their wild type counterparts⁶.

KChIP1, 3, and 4 are mostly expressed in the brain while KChIP2 is expressed in the heart as well as in the brain^4-6.