Perhaps the sister was created by the same mutagen as the turtles but was separated from them. When she finally finds her brothers, there could be some initial distrust and confusion. But as they get to know each other, she becomes an important part of the team. She might have a different personality compared to the turtles, like being more diplomatic, which could help in dealing with some of the more complex situations they face, such as negotiating with other mutants or humans who are not immediately hostile.
It could be Shredder as always. He might see the sister as a new threat or a way to get to the turtles. He could try to kidnap her to lure the turtles into a trap.
Maybe the human sister is a scientist who is working on a project that could potentially help the Ninja Turtles in their fight against evil. But the bad guys find out about it and try to stop her. Or she could be an artist who uses her art to inspire the Turtles and give them new ideas for their strategies. She might also have a secret past that is somehow connected to the mutagen that created the Turtles.
Krang from Dimension X could also be a great villain. He might be interested in the human sister because she has some unique knowledge or ability that he wants to use for his own evil plans in taking over Earth. He could send his minions to capture her and the Turtles would have to journey to Dimension X to save her.
One possible plot could be that the turtles are exposed to a strange mutagenic substance that starts to reverse their mutation and gradually turn them human. They then have to deal with the challenges of living as humans, like going to school and fitting into society while also trying to hide their former turtle identities from those who might not understand.
One idea could be a human character who discovers the Ninja Turtles' lair by accident and has to prove they can be trusted. Maybe they help the turtles in a battle against a new enemy, like a mutated creature from the sewers that the turtles hadn't faced before.
You can try looking for them at your local comic book store. They might have a good selection.
One idea could be a story where the Teenage Mutant Ninja Turtles discover a hidden mecha technology in the sewers. They have to figure out how to use it to defeat a new, powerful enemy. Maybe it gives them new abilities like enhanced speed or the power to fly.
In a short story, the plot could be that the Ninja Turtles are invited to a martial arts tournament in another dimension. They travel there and find that the rules are very different. They have to adapt quickly. However, they soon realize that it's a trap set by an old enemy. The enemy has brought some of their toughest foes from different dimensions to fight them. The turtles must use their wits and their martial arts training to defeat all these opponents and find a way back home.
One idea could be exploring the turtles' origin in more depth from a different perspective. Maybe a new character discovers a hidden aspect of their mutation process.
In this fanfiction, perhaps the turtles get captured because they walked into a well - laid trap. Their friends like April could be trying hard to rescue them. She might use her skills and connections in the city to find out where they are held and then plan a rescue mission. It could involve a lot of sneaking around and fighting against the captors' minions.