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- Krysten Ritter plays the titular Jessica Jones, a private detective with superpowers.
- Mike Colter plays Luke Cage, Jessica's love interest and a superhero in his own right. In the Jessica Jones comics, Cage owns his own bar, and it seems like he may in the show as well.
- David Tennant plays Kilgrave, a villain with mind-control powers, known in comics as the Purple Man.
- Carrie-Anne Moss will be playing an original character, so far known only as Harper.
- Rachael Taylor will play Trish "Patsy" Walker, Jessica's best friend and, in comics, the superhero Hellcat.