Tribute Cover!
This is the famous story where Deadpool teleports through various alternate realities, gets cloned, fights Apocalypse (with the help of X-Force), and protects baby Cable from Mr. Sinister. Deadpool’s mind supposedly gets “fixed” but he’s not much different afterwards.
Deadpool wants to die because he essentially learned recently that he is programmed to kill and will never be able to successfully overcome that programming. He goes to the villain Black Box for help, but instead of teaching Wade how to commit suicide, he triggers Deadpool’s programming and pushes him to kill all the supers in the world. Starting with Cable.
Using their bodyslide connection, Deadpool finds and kills a bunch of alternate Earth Cables.
One of these is the “House of M” universe, so this arc ties into that bigger event, and the end of House of M brings an end to this arc, reuniting Cable and Deadpool…Only Cable is now an infant.
As such, he pees on Mister Sinister.
Forge invents a way to grow baby Cable back up.
But once Cable is an adult, it triggers the Black Box brainwashing. But rather than kill Cable, Deadpool shoots himself in the head.
This enables Cable to use his powers to heal Deadpool—at great personal cost. The aftermath issue, #19, has Cable’s body growing and Deadpool trying to get him laid during his teenage years by going to Intercourse, Pennsylvania, but also lots more about the Cable vs Deadpool ongoing love/hate bromance and we essentially end where we started, at status quo.
There’s also a fairly extensive “false origin” for Deadpool, showing his experiences as a child that may or may not be true because, we’re reminded, Deadpool is literally crazy and his memories are wholly unreliable.
Deadpool working for a villain to kill heroes (albeit alternate reality heroes) is why this is titled, “Enema of the State”—it’s riffing on the story (see tag below) where Wolverine was brainwashed by Hydra to kill off superheroes.