Abstract It is now widely accepted that acetylcholinesterase (AChE) also displays non-cholinergic functions, completely independent of cholinergic transmission. Indeed, AChE has been implicated in a variety of trophic and toxic actions in a range of different systems. However, it is still uncertain what part of the AChE molecule may be responsible for these actions, and indeed via what receptor. Recent work has identified a peptide towards the C-terminus of the AChE molecule that appears to have very similar effects to non-cholinergic AChE itself. This action is to enhance calcium entry, in acute and chronic preparations across a trophic–toxic spectrum, depending on concentration applied and/or duration of exposure.