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Friends

Donatello: Out of all the Turtles, Donnie is the one April is closest with. He has a HUGE crush on April, and fell in love with her at first sight. He is also the one that instigated the rescue of April and father from the Kraang, and who saved her from the Kraang's getaway copter at the end of the episode Rise Of The Turtles. He has tried numerous times to get her attention, but April is either indifferent or oblivious to his advances. She does, however, seem to care about him as a friend. April kissed Donnie on the cheek in Target: April O'Neil and The Lonely Mutation of Baxter Stockman three separate times as a way of saying thank you to him, as well as once on the lips in A Foot Too Big to make him feel better and in the episode In Dreams on his cheek to show that she was relieved that he's okay. However, despite this, April probably does not have a crush on Donatello in the same way he does her, consistently showing more interest in Casey (however infuriating she may find him) and being polite-but-clearly-a-little-uncomfortable when Donatello calls her (for example) "my sweet princess" or gives her gifts (such as the music box in A Foot Too Big).

Leonardo: Aside from Donatello, Leo appears to be the most protective of April in the group and is supportive of her efforts to discover information that will lead them to find her father. Leo, aside from Donnie and Splinter, has been the most to interact with April.

Raphael: As of yet, Raph and April have not interacted much onscreen. He does, however, seem to show deference to her when she catches him and his brothers teasing Donatello for sustaining injuries from a lab monkey or when he laughed at her for being chased by Pete, a giant Pigeon. However, they do remain good friends, and Raph shown signs that he cares about her at least as much as Leonardo and Michelangelo do (as seen in Panic in the Sewers where he agreed with the others that she shouldn't go spying on the Foot, and in Karai's Vendetta when she spilled Kraang water on herself). He is also the one that goes to rescue her in The Kraang Conspiracy, though both he and April make satirical comments about it. Most notably are the handful of occasions when Raphael refers to April as "sister" when making a sarcastic comment, and one point in Race with the Demon! where April put her arm around his shoulders. Raph and April do seem to get along most of the time, probably because both have very feisty, active personalities. Whilst Donatello clearly has a crush on April, Raphael is more like a big brother to her.

Michelangelo: Mikey and April have not interacted much onscreen. Although she is his first human friend, Mikey says she doesn't really count because she is obligated to like him since he helped to save her life. Despite all that, they remain good friends and Mikey Cares about her. Examples are shown in The Gauntlet Where he offered to make April some soup or get her a tissue when she was upset over the fact Pete was after her. He even was the first to object to using April as bait. They have a distinct older sister/little brother relationship, as even April can get annoyed by his childish antics, but is as quick as Raphael to make sure Mikey is okay.

Master Splinter: Since April's Father has been captured, Splinter has become a surrogate father to April. He has noticed her innate sensitivity to her surroundings and has begun to train her as a kunoichi or female ninja in the episode Baxter's Gambit, though it was implied that she had already begun training with him back in Panic In The Sewers. Giving April the Tessen meant for Miwa was the first clear point that their relationship is very like Splinter's with the turtles; a father and his child as well as a teacher and his student.

Karai: April met Karai in person at Murakami's Noodle Shop in Karai's Vendetta, when Karai was sent by Shredder to find her. When April tried to beat her in hand to hand combat but failed, she manages to defeat her when she reveals that her mother dies, causing Karai to hesitate feel pity for her, and April successfully pushed her down the stairs of a subway station, which impressed the Turtles that she was able to fight against a professional kunochi and not get killed in the process. At some point April may have been slightly jealous of Karai for having superior fighting skills, given that the turtles often asked her (April) to be look out whereas they had no such qualms with Karai fighting beside them (trust issues aside). Similarly, April was clearly irritated when Donatello accidentally implied April was not a "real kunoichi" like Karai. April possibly felt pity for Karai in return after learning that Karai is actually Miwa, the very same daughter of Splinter's by Tang Shen whom April's Tessen was suppose to go to before Shredder took her. However, like Raphael, she was skeptical as to whether this was enough for Karai to turn over to their side of the battle. In The Wrath of Tiger Claw, when Karai went after April while Tiger Claw went after Casey, April pulled out the Tessen to fight, but Karai insisted for April to listen. When Donnie and Leo came over to attack, April stopped them because she believed her, implying she may trust her now.

As the series progresses, April and Karai become good friends and allies who trust each other and got each other's backs.

Casey Jones: April and Casey seem to care about each other a lot. Casey, like Donatello, has a crush on April, much to Donatello's irritation. At first, April was Casey's trig tutor, and after some time they became good friends. When Mutagen Man attacked them, Casey became protective over April and vice-versa when she saved him. When a squadron of Robot Foot Soldiers attacked them at the Midtown hockey rink, April somehow ended up leaving Casey behind and ran out of the rink as Donnie came to her rescue. Afterwards, she remembered about Casey and they rushed back to the rink to find him perfectly alright. In Wormquake! when Casey was eaten by a one of the giant space worms, April was distraught when he was thought to be dead. Similarly, she was (understandably) immensely relieved when he was revealed to be still alive, and ecstatic when she and Donnie saved him from the worm. Although it was revealed that Casey prefers to hang alone with April (mostly because of Donatello's hanging around April), he is seen to hang out with her and the turtles in many episodes, and even hanging out with the turtles without April around (usually Raphael or Donatello). One of the main reasons for April's closeness with Casey is that she can talk about the turtles and Splinter with him. Casey's rivalry with Donatello irritates her to no end, but when it is resolved she seems to be a little apprehensive as to whether the absence of said rivalry is an improvement or not.

Pigeon Pete: April's dad sent Pete to deliver a message from him warning her about the Kraang's mutagen bomb. In return, April asks him where the Kraang are holding her dad, for she won't leave the city without him.

Dr. Tyler Rockwell: April developed a soft spot for Rockwell when he attacked her and Donnie while they were investigating his disappearance. It was revealed through her half-Kraang powers that that the mutant chimpanzee she and the Turtles were up against is Rockwell and that his colleague Falco has more to tell about the experiment with Mutagen.

Enemies

The Kraang: The Kraang have been enemies of April since the beginning of the series. They attempted to abduct her and her father, but when the Turtles saved her, the Kraang already got away with her father. In TCRI, when the Turtles reveal that they learned from her father that, the Kraang have been kidnapping scientists to help modify their mutagen's properties, April became confused and revealed what kind of scientist her dad is: a psychologist, which means that his area of expertise would have nothing to do with the ooze. This confusion ended in shock when Mikey showed them a Kraang storage device he stole that revealed that the Kraang's intended target was actually April. The reason why is revealed in The Kraang Conspiracy, when Jack Kurtzman reveals that the Kraang had been trying for centuries to experiment on the birth of the perfect human with a "specific chain of human DNA" they need for their invasion and to perfect the mutagen, eventually finding their success on April's mother. Donnie later studied April's DNA to see how this "specific chain" is possible, which is a total shock that it was when he found traces of Kraang DNA in it and concluded that this is why April has her strange immunity to Kraang water and mutagen, which only a Kraang could have, as well as her DNA's use as an ingredient for retromutagen: because April is a half-human, half-Kraang mutant.

Shredder: Shredder learned from his Kraang hostage that April is not only a friend of the Turtles, but also the ingredient to the Kraang's invasion that the Turtles are guarding from the Kraang, so with the Kraang's help, he uses her as bait to lure Splinter out of hiding. Due to this, it is quite probable that April dislikes him greatly.

Tiger Claw: Since April was responsible for the Kraathatrogon swallowing him, Tiger Claw returns with a possible hatred for her and since he hates the Kraang, as April is part-Kraang, he'll probably stop at nothing to kill her.

Stockman-Fly: April was kidnapped by Stockman-Fly as part of his backup plan for the hope of Donnie giving him the retromutagen, which is to merge with her through mutagen and become one. However, because of her Kraang DNA, April is immune to the mutagen.

Bebop: April was sometimes treated much like a lady by Bebop when he intends to trip her instead of hurting her.

Chrome Dome: Though it was originally programmed by Karai to help her kill April, Chrome Dome's programming was unexpectedly changed by the Kraang to capture her for them, shocking April and the Turtles that the Kraang are still after her and angering Karai.

Snake / Snakeweed: April's relationship with Snake is unknown at most part, but she probably dislikes him after he helped the Kraang kidnap her dad.

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