Among the multiple roles assigned to calmodulin, controlling the surface expression of Kv7.2 channels by binding to two discontinuous sites is a unique property of this Ca2+ binding protein. Mutations that interfere with calmodulin binding or the sequestering of calmodulin prevent this M-channel component from exiting the endoplasmic reticulum, which reduces M-current density in hippocampal neurons, enhancing excitability and offering a rational mechanism to explain some forms of Benign Familial Neonatal Convulsions (BFNC). We previously identified a mutation (S511D) that impedes calmodulin binding while allowing the channel to exit the endoplasmic reticulum, hinting that calmodulin binding may not be strictly required for Kv7.2 channel trafficking to the plasma membrane. Alternatively, this interaction with calmodulin might escape detection and indeed, we now show that the S511D mutant contains functional calmodulin binding sites that are not detected by classical biochemical techniques. Surface expression and function is rescued by calmodulin, suggesting that free calmodulin in HEK293 cells is limiting and reinforcing the hypothesis that calmodulin binding is required for ER exit. Within the calmodulin binding domain formed by two sites (helix A and helix B) we show that calmodulin binds to helix B with higher apparent affinity than helix A, both in the presence and absence of Ca2+, and that the two sites cooperate. Hence, calmodulin can bridge two binding domains, anchoring helix A of one subunit and to helix B of another subunit, in this way influencing the function of Kv7.2 channels.