Los Angeles - Deadpool director Tim Miller reportedly quit the sequel over the casting of Cable.
According to The Wrap, Miller wanted Kyle Chandler for the role of the time-travelling mutant - Deadpool's friend and foe in the comic books - but star Ryan Reynolds disagreed.
When the studio chose to back Ryan, Tim is said to have decided to leave the project.
It has also been claimed that they disagreed on their vision for the film, with Miller arguing for a "more stylised sequel" while Reynolds wanted to return to the "raunchy comedy style" of the first movie.
Deadpool 2 has yet to be handed an official title or release date, but is being scripted by Rhett Reese and Paul Wernick, who penned the first movie.
And Ryan and the film's other producers are reportedly trying to cast the film's female lead, the Marvel mutant Domino.
Sienna Miller, Ruby Rose, Lizzy Caplan and Sofia Boutella are among the actresses who are rumoured to have tested for the coveted part.
Meanwhile, producer Simon Kinberg recently gave Marvel fans an insight into what they can expect from the new film, irrespective of who directs it.
He said of the sequel: "I think Deadpool 2 will comment on anything that's happening in movies today especially in superhero movies. The sort of glut or saturation of these movies and the proliferation of sequels is definitely something we'll play around with."