BK (K_Ca1.1) channels are critically involved in diverse physiological processes in both electrically excitable and non-excitable cells.

Leucine-rich repeat containing protein 26 (also known as BK channel auxiliary gamma subunit or LRRC26) is a single spanning transmembrane protein of ~37 kDa. LRRC26 protein contains five major leucine rich repeats in its extracellular domain which are all required for modulating BK channel activity. The single transmembrane segment of LRRC26 is required for co-assembly with the BKα subunit complex.

When LRRC26 is acutely knocked down in LNCaP cells, the voltage-dependent activation of endogenous BK current shifts from a low to a high V_1/2 value, whereas recombinant expression of LRRC26 cDNA in naïve cells (such as PC3 prostate cancer cells and HEK 293 cells) normally lacking LRRC26 shifts BK channel activation from high to low V_1/2 values, reproducing the channel behavior observed in LNCaP cells. This findings indicate that LRRC26 is sufficient to impart low voltage gating behavior to wild-type pore-forming, BKα subunits.

LRRC26 lowers the energy barrier for activation of BK channels, and is able to stabilize channel opening in response to voltage, thereby maintaining channels in the open state to a much greater extent at any given membrane potential¹.

LRRC26 is expressed in cerebral artery myocytes where it is primarily plasma membrane localized and associated with BKα subunits. LRRC26 serves as an arterial myocyte BK channel auxiliary γ subunit that elevates voltage and apparent Ca²⁺ sensitivity to induce vasodilation².