Ma was the matriarch of the Gnucci Crime Family, a Mafia-like group that appeared to have majority control of illegal activities in New York. As such, she had subtle control over both the mayor and the police commissioner. Other members of the Family included Ma's brother, Dino and her three sons - Eddie, Bobbie and Carlo.Frank Castle killed Ma's sons in order to re-announce his presence to the New York underworld. Ma hired a number of vigilantes to try and eliminate Punisher out of vengeance, but the Punisher outsmarted all of them and took the money Ma offered as a down payment. Frank intended to "wear down Ma's defenses" before actually killing her, thus he spent the next several weeks attacking Gnucci soldiers.
Finally, Frank gunned down Ma's brother Dino after a run-in with Matt Murdock. The very next night, Ma and a few of her remaining soldiers found Frank Castle outside the Central Park Zoo. Despite being outnumbered and virtually unarmed, Frank managed to fight them off, killing all the soldiers and feeding Ma to a pack of polar bears.
Ten days later, Ma was still alive, having lost both arms and legs while being horribly scarred. Understandably, she was much more disturbed. When one of her cousins asked her "how she is" after her mauling, she ordered one of her men to shoot her cousin. When that man hesitated, she ordered another man to shoot her cousin and the first man. When that man hesitated, she ordered a third man to shoot her cousin and the first two, and so on until three of her men and her cousin lay dead at her non-existent feet. She put out a $10 million bounty on the Punisher's head, and contacted the Russian in order to ensure Frank Castle's defeat.
When the Russian arrived, Ma sent him to the Punisher's reported hideout. In the meantime, Ma was informed that she would not receive any more help in fighting Frank Castle, who had killed eighty of her soldiers in less than two weeks. Anticipating victory, Ma was shocked to see Frank appear on her front lawn holding the Russian's head. The remainder of her soldiers threw down their guns and left, saying that she "can't pay us enough to fight that." Frank then burned the Gnucci house to the ground (after raiding a safe and stealing some of Ma's money and secret documents) with Ma inside. 
Six years later, it appeared that Ma Gnucci had mysteriously come back from the dead. However, her mysterious resurrection was discovered to be part of a master plan of revenge against the Punisher; masterminded by the son of the deceased high-society vigilante, Elite.
Ma Gnucci's nephew Peter realized he stood to inherit Ma's money, if the Punisher died. He hired Deadpool to kill him. When it was falsely assumed the Punisher was dead, Peter acquired his money in the form of a check. He lost it in traffic. By the time he realized he can ask the bank for a new one, it was too late. A truck bounced him out of the road and impaled him on the Wall Street Bull statue.
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- 15 Appearances of Isabella Carmela Magdalena Gnucci (Earth-616)
- 3 Minor Appearances of Isabella Carmela Magdalena Gnucci (Earth-616)
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