The KCNK16 gene encodes the TALK-1 channel, an abundant K⁺ channel transcript found in mouse and in human β-cells. There are four human TALK-1 transcript variants, including two that form functional K⁺ channels (TALK-1a (transcript variant 2) and TALK1-b (transcript variant 3)^1,2. The TALK-1 structure includes 4 transmembrane domains, 2 extracellular loops, and intracellular N- and C-termini. The C-terminal tail of TALK-1 is a critical component that influences the magnitude of TALK-1 channel activation, while the N-terminus is important for protein interaction^1,2.

TALK-1, two-pore domain K⁺ (K_2P16.1) channel is responsible for modulating glucose stimulated insulin secretion that relies on β-cell Ca²⁺ influx. The channel produces outwardly rectifying, non-inactivating K⁺ currents, which are enhanced by elevations in extracellular pH. TALK-1 is thus pH-sensitive, with increased activity under alkaline conditions. In addition, it can be activated by singlet oxygen and nitric oxide.

A gain-of-function polymorphism in the KCNK16 gene is associated with increased risk for developing type-2 diabetes^1,2.