I wouldn't recommend remapping the scroll wheel as a hotkey. If you're set on doing it, go ahead, but it's at your own risk. Let me explain why.
The rule is clear: buttons on your gaming mouse or keyboard can generally be used as hotkeys. However, the mouse wheel or scroll mechanism is not a button. While some mice provide a middle-click feature (triggered by pressing the scroll wheel), this is technically distinct from the scroll action itself, which serves as a continuous or incremental input mechanism.
From a technical standpoint: there are significant differences in how scroll inputs and button inputs are processed at the hardware, driver and OS levels. Scrolling functions as a continuous input mechanism, producing incremental or continuous signals based on movement, whereas a button produces a discrete input, generating a single signal per press. The act of using the scroll wheel inherently results in multiple actions per movement, with each scroll tick treated as an individual signal.
And why this differs from holding a keyboard key?
When the scroll wheel is remapped to emulate a button, such as to type the letter "A" each scroll tick or motion produces a separate key-down and key-up pair. For instance, a single rotation of the scroll wheel, which results in multiple ticks, could produce an output like "AAAAAAAAAA". The high frequency of these events causes input overload because the scroll action bypasses the OS's (and the game client) keyboard delay and repeat rate logic.
This differs from holding a keyboard key because keyboard inputs follow a specific delay and repeat logic enforced by the operating system/game client. When a key is held, the system processes an initial key-down event, waits for a configurable delay, and then generates repeated keypress signals at a fixed, controlled rate. In contrast, the scroll wheel produces independent events for each tick or motion, bypasses the delay and repeat logic entirely, and treats each tick as a unique event.