The 78-year-old actor grew emotional as he discussed the passing of his close friend and his wife Michele Singer Reiner - who were killed in December - and admitted there have been multiple times since the tragedy that he's gone to call the director for a chat.
Speaking on The Late Show with Stephen Colbert, Crystal - who has two daughters with wife Janice - described Rob as "hilarious, devoted, (and) opinionated in the best way" and someone who was always "fighting for our truth, for our country."
"(He had) the greatest comedy taste. We could talk about everything. He was an uncle to my kids … There's so many moments … when something good happens — or 'Isn't that crazy?' — I want to pick up the phone and call him. Because that's what we would do.
"It's a profound loss for… I'm just gonna say humanity, because he was the most human person that I ever met."
Crystal met Reiner in 1975 when they starred together in All In The Family and he recalled how he and his friend were reflecting on their lengthy careers shortly before he died.
"We had spent the night before together and [were] talking about our careers together," he said.
"We were talking about the movie business and how it's changed and how people don't go to theatres like they used to.
"We talked about the fact that you can't control how a movie is going to do. What you can control is the experience of making it.
"He said, 'That's something you always have.' Hits are great to have, but it's the people that you hold on to. I kept that in my heart."
At last month's Oscars, Crystal led a tribute to Reiner alongside a number of stars who had worked with the This Is Spinal Tap filmmaker throughout his career, and the City Slickers star revealed he had called host Conan O'Brien with the idea for the spot.
"His first seven movies were incredibly different and so great," he said.
"I can get the cast of those movies together to walk out with me, that would have made him really smile.
"So I got in touch with all of them. The Academy was great in getting most of them there. … We were able to hold hands and walk out there in tribute with a beautiful picture of Rob and Michelle because they were our closest friends."
Rob and Michele's son, Nick Reiner, has been charged with their murders but has pleaded not guilty.
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