"Grace and I have two beautiful children together," De Niro said in the statement to ET. "We are entering a period of transition in our relationship which is a difficult but constructive process. I honor Grace as a wonderful mother and ask for privacy and respect from all as we proceed to develop our roles as partners in parenting."
De Niro, 75, and Hightower, 63, met in 1987 and tied the knot 10 years later. They briefly split in 1999, but never finalized their divorce, choosing to renew their vows in 2004. They also share two kids together -- son Elliot, 20, and daughter Helen, 6.
De Niro also shares son Raphael, 42, with his first wife, Diahnne Abbott, and twin sons Aaron and Julian, 23, with his former girlfriend, Toukie Smith.
Hear more on De Niro and Hightower's breakup in the video below.