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Lisa Marie Loud is the second-youngest of Lincoln's sisters in The Loud House. In spite of only being four years old, Lisa is the smartest of the eleven siblings, having already worked gotten a PhD and won the Nobel Prize. Speaking with a lateral lisp, Lisa spends her time invested in research, projects, and working on complex experiments, which often involve using her siblings as test subjects.

Before the beginning of the series, Lisa, despite her very young age, is a Junior Nobel Prize recipient. Though she is still in kindergarten, she is exceedingly smarter than the other kids her age, nonetheless, that she can move up at least six grades.

Though the second-youngest of the Louds, Lisa is a child prodigy, so she's the smartest kid in the bunch. Because of this, she often tends to be egocentric, boorish, condescending, and sarcastic with other people. She speaks with a lateral lisp, and usually has a stoic frown, though she does smile from time to time.

She is not as excited as her siblings, although sometimes she becomes in that state when something really good happens, like when she and the other sisters discover about Lincoln's romantic situation in "Heavy Meddle". She states this is because she does not partake in mundane human emotions as stated in "Heavy Meddle". She was also shown to have fallen for Hugh like all of her other sisters, and showed a more immature side to her, at one point having Hugh show off his six pack under the lie that she was teaching Lola human anatomy with him as an example. She also became somewhat irrational, claiming she would marry Hugh, and have children with him, despite the obvious age difference, and following him around like her other sisters. She also does not believe in superstition, fortune telling, blessings or curses as she is a realist and believes only in science as stated in "Raw Deal" and "Study Muffin". However, she believes in aliens, as she claimed in "Friend or Faux?". Nonetheless, she likes to be with her siblings and have fun with them, even if she doesn't express it.

In many episodes, she can be seen working on strange experiments. In "Left in the Dark", she creates an Oreo shaped cookie called "Gloweos" with the infused DNA of a jellyfish, and if someone ate it, all of his/her body will glow. One of her favorite hobbies is resolving very difficult math problems. She also likes to study the poop and bathroom habits of her siblings, something they all find gross and annoying.

As seen in "Overnight Success", Lisa not only likes to realize experiments with her siblings, but she also likes to realize them with people outside of her family.

Though easily the most mature of her siblings, she can also be quite mischievous and sneaky. For the most part her pranks are hidden in unassuming objects; such as acne cream, sunscreen, mouthwash, etc, with results like turning skin blue, mild sunburns, and hot-pepper induced fever, respectively. Lisa is also completely willing to join in the madness caused by her siblings, whether it be disputes over money, the "sweet spot", or just playing along. This proves that while Lisa is a genius, she's still a kid and acts her age.

Contrasting most of her family, Lisa is very honest and blunt about what is on her mind. Lisa's brutal honesty isn't so much out of a sense of morality, but because she doesn't want wasted brain space by making up a lie. This also makes her incapable of keeping a secret. Like Lincoln she's very individual in contrast to rest of the sisters as seen in "It's a Loud, Loud, Loud, Loud, House".

Lisa, like her polar opposite Leni, is ironically very scatterbrained. She can frequently forget crucial ingredients to her various experiments, which can lead to devastating, though hilarious, outcomes. She also frequently forgets to look up while reading while walking, much to her embarrassment, and tends to misplace her vials, test tubes, and chemicals.

As seen in "Party Down" Lisa appears to have a fun side. As she gets a sugar high from having too much chocolate from a chocolate fountain. This proves that Lisa isn't a complete no nonsense person and can loosen up and act her age.

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