KChIPs belong to the family of small cytosolic calcium-binding proteins and consist of four different KChIP isoforms ranging between 216 and 270 amino acids. They all have a reasonably conserved core region of 185 amino acids and a heterogeneous N-terminal. KChIPs have calcium-binding EF hands which appear to be important for modulation of K_V channels but not for Ca_V channels¹.

The cardiac KChIP2 gene generates three protein isoforms of 220, 252, and 270 amino acids via alternative splicing of exons 2 and 3. It is well established that KChIP2 functionally increases peak K_V4 current, slows channel inactivation and accelerates recovery from inactivation. Furthermore, KChIP2 has been reported to increase I_Ca,L and suggested to decrease K_V1.5 cell surface expression and facilitate I_Na² .

All four KChIP mRNAs are found in the brain, however only KChIP2 is expressed in the heart³. KChIP2 is expressed heterogeneously across the canine and human left and right ventricular free wall with higher concentrations in epicardium compared to endocardium⁴.

Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2^−/− mice are highly susceptible to the induction of cardiac arrhythmias⁵.