The actor played Hal in "Proof" Off-Broadway at MTC and then on Broadway where he and the entire company were nominated for Tony Awards.
He followed that up with the role of neurotic Louis in the award-winning HBO film, "Angels in America."
Playbill On-Line said Shenkman will now replace Liev Schreiber in the MTC revival of Donald Margulies' play about questions of identity and authenticity in the 1980s art world.
Schreiber reportedly bowed out of the Broadway run at the Biltmore to direct a film.
Previews for "Sight Unseen" begin May 6, with an opening night planned for May 25.
Co-starring in the play will be "Mystic River" and "Love Actually" star Laura Linney, who appeared in the original 1992 New York run of the play in a different role.