Supergirl finally introduced Lex Luthor, setting him up as the big bad of season 4. While many predicted this development as soon as it was announced that actor John Cryer had been cast in the role, few could have anticipated just how well he would play the part of Superman's arch-enemy. Fewer still guessed just how deeply and from what sources his introductory episode, "O Brother, Where Art Thou?", would draw upon in crafting the most comics-accurate vision of Lex Luthor in years.
Surprisingly little has been said about Lex Luthor in the world of the Arrowverse to date. His sister Lena Luthor was introduced as a regular member of Supergirl's cast in season 2, with Lena attempting to redeem her family's name and their company in the wake of Lex's incarceration on a variety of charges. It was said that Luthor and Superman were once friends who had worked together to repel hostile alien invasions of Earth, but that Lex's more violent methods did not sit well with Superman and Luthor eventually grew to resent Superman's popularity with the public when the industrialist felt he was doing all the real work. This grudge eventually led Luthor to blame Superman for attracting the attention of dangerous alien criminals and to devote his life to destroying his former ally.
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Supergirl season 4, episode 15 opens with a flashback to the spring of 2015, showing that Lex was arrested after somehow turning Earth's sunlight red in a bid to depower Superman. When the story returns to the modern day, Lex has just been transported to Luthor Manor. After having a stroke in prison and being determined to have developed inoperable cancer after injecting himself with Kryptonite as part of his efforts to keep Superman away from him, Luthor is allowed to serve the rest of his sentence under house arrest. It is here that he begins badgering Lena to test a wonder-cure she is developing using a Kryptonite derivative called Harun-El on him, figuring he has nothing left to lose.
All of these concepts are taken directly from the original Superman comics, where Luthor discovered that Kryptonite radiation was deadly to humans (if not quite so fast-acting as it is with Kryptonians) after he began wearing a ring made of Kryptonite to keep Superman at bay and later developed cancer. He also briefly turned the sun red in a bid to save Earth from an invasion of hostile Kryptonians during the War of the Superman storyline in 2010. The show even managed a clever nod to DC Super Pets and the Krypto the Superdog show, with Lex telling Lena a story about a dog named Ignatius he owned before she was adopted into the Luthor family; Lex has a pet named Ignatius in both realities, though those pets are iguanas rather than dogs.
It is Jon Cryer's performance as Lex, however, which sells the character. While many suspected that Cryer's joining the cast of Supergirl was purely a casting stunt (Cryer infamously played Lex Luthor's nephew Lenny Luthor in Superman IV: The Quest For Peace), few were left picturing Cryer as a bald, bearded Alan Harper by the episode's end. Cryer's performance seemed to draw deeply from both Gene Hackman's performances as Lex Luthor opposite Christopher Reeves' Superman and the popular image of Luthor from the comics as a sarcastic show-off who can't help but flaunt his intelligence and his superiority. For instance, even while suffering a seizure under the watch of an utterly indifferent government agent, Lex can't help but compare himself to Jesus of Nazareth, muttering "Don't blame him. He knows not what he does," before dryly adding "He's on a government salary, after all."
In this, while Cryer's Luthor might be compared to his character from Two And A Half Men in having a similar humor, that is the only way in which Cryer will remind viewers of his most famous role in modern television. It will surprise no one that Lex is able to cure his condition by the episode's end after hijacking his sister's research and is able to effortlessly kill his handlers with the mansion's secret defenses. The episode ends on a cliffhanger, with Lex staring down a newly arrived Supergirl, as he is escaping Luthor Manor by helicopter, suggesting a big battle to come next week.