Mutations to the GxGD protease presenilin are associated with Alzheimer’s Disease (AD). A molecular basis linking presenilin mutations to AD is modulation of the intracellular calcium leak. There are contrasting views as to how calcium homeostasis is altered by presenilin, and it is not generally thought that proteases can have dual functions as ion channels. We therefore investigated if ion channel activity is present in the GxGD proteases, PSH and FlaK. We took advantage of the published crystal structures of both of these proteins, and used them as surrogates to investigate whether proteases, and by extension, presenilin are ion channels. We demonstrate that PSH and FlaK form ion channels in lipid bilayers. A mutation that affected the enzymatic activity of FlaK, however, rendered the channel catalytically dead and altered ion selectivity, indicating that ion channel and catalytic activities are linked. We conclude that PSH and FlaK are “chanzymes”, with interdependent ion channel and protease activity conferred by a single structural domain embedded in the membrane. Our data support the proposal that higher-order proteases, including presenilin have channel function, and support a link between disruption of presenilin calcium channel activity and AD