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The fundamental role of HVCN1 is to pump out protons, thereby increasing the intracellular pH. The channel is exclusively selective for H⁺ and opens upon membrane depolarization, although its open state hugely depends on the pH on both sides of the membrane. Its role is best described in leukocytes where phosphorylation via PKC on a Thr residue potentiates the activity of the channel and increases its open state, thereby increasing the H⁺ current across the membrane, in this manner mediating optimal NADPH-oxidase (whose optimal activity is at pH 7.5) required for the production of reactive oxygen species (ROS) necessary for phagocytosis to occur.