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Derek and Lizzie have an unspoken "live and let live" policy.
He does mention in "When Derek Met Sally" that he likes being her step-brother.
In an episode where Derek finds out that Casey's new boyfriend is cheating on her, Derek is quick to rescue Casey and reveal what a jerk her boyfriend is.
Through the whole episode, he is pondering whether to do "the right thing" to help Casey, and in the end, he does.
In the episode "The Fall", Derek insists he's only helping Casey's rep because if she looks bad, he looks bad, but it's made pretty obvious that Lizzie's statement, "She's your sister too," actually got to him.
He also bails her out of trouble in "The Poxfather".His younger brother Edwin Venturi is his trusted accomplice and lackey.