But while on The Owl tour with the band in 2019, the musician noticed something was off with his bass playing — the very thing he'd devoted his life to.
"It wasn't that I couldn't play anymore, it was that I couldn't play as fast," Hopkins tells PEOPLE in this week's issue, on newsstands Friday. "My guitar hand was failing me."
He also noticed that his speech slurred at times, and he was having trouble "scooting" around, as he describes it, on stage.
"I'm not Justin Timberlake, but I'm a rock and roll guy and can dance pretty well," says Hopkins, 51. "Jumping started to bother me."
Over the next two years, Hopkins visited multiple neurologists and specialists looking for answers. Finally, in December 2021, just days before Christmas, doctors in Atlanta — where Hopkins lives with his wife of 14 years, Jennifer, 50, and their three young daughters — had him do an electromyography (EMG) test to determine whether there was damage in the nerves that control his muscles.
Diana King John Driskell Hopkins
The results of the test determined a devastating diagnosis: Hopkins had ALS (amyotrophic lateral sclerosis) — a degenerative disease that causes progressive paralysis of the muscles responsible for chewing food, speaking and walking. It eventually leads to complete respiratory failure, usually within five years.
"In my life, I've been scared, I've been angry, I've been stressed," says Hopkins. "But I don't know that I've ever truly felt anxiety until that day."
When a subsequent EMG done at the ALS clinic at Massachusetts General Hospital also determined Hopkins had ALS, "it was devastating," says Jennifer. "In that first month, I spent a lot of time in my closet and the shower crying because I didn't want our daughters to see me that way."
While Dr. Richard Lewis, an ALS specialist and the director of the Electromyography Laboratory at Cedars-Sinai hospital in Los Angeles who has not treated Hopkins, says ALS can be "relatively rapid" with an average three to four-year progression, people can also "live 10 to 15 years with ALS."
In the five months since his initial diagnosis, Hopkins has made his peace with the unknown ahead of him.
"No one knows what the condition will be like going forward, so we can't sit around and cry about it," says Hopkins.
Though he's coping with weakness and balance issues, Hopkins has otherwise managed to maintain a demanding schedule since his diagnosis. On April 22, he joined Zac Brown Band on their seven-month "Out In The Middle" tour.
"I'm singing as well as I've ever sung, and I was never a good player," he says jokingly. "The band will back me up on that. When I told them about my diagnosis on a Zoom call, Zac said, 'Are you making all this up because you're a s—ty banjo player?'"
Ethan Miller/Getty John Driskell Hopkins
On Friday, Hopkins and Jennifer also launched Hop On a Cure, a foundation dedicated to raising funds to find a cure for ALS, which approximately 5,000 people are diagnosed with each year.
"Our vision is clear," says Hopkins. "We need to do everything we can to generate funds to cure ALS."
Adds Jennifer: "We want to prevent anybody else from being told they have ALS and there's nothing that can be done."
Raised in Gainesville, Georgia, the son of mom Joan, a teacher, and dad Ralph, a radiologist, Hopkins started singing in church choirs and playing piano and guitar as a kid. He graduated from Florida State University with a degree in general theater in 1993, and in 1998, he met Zac Brown, then an aspiring singer, while hosting an open mic night at a local bar.
The two stayed close, and in 2005, Hopkins joined Zac Brown Band, whose breakthrough hit "Chicken Fried" came in 2008. Since then, Hopkins has spent a lot of time on the road with the band, living "on beer and pizza," he says.
So, when he first started experiencing symptoms, he chalked it up to age. "At 48, you just say, 'Ah, I can't jump anymore,'" he says. But when his symptoms worsened, Jennifer says they knew they had to "dig deeper."
Since his diagnosis, Hopkins has adopted a gluten and dairy-free diet — minus the piece of strawberry shortcake on his birthday on May 3. "You got to be reasonable!" he says.
Alongside the "38 pills" he takes daily — a mix of supplements and traditional ALS medications — he also follows a naturopathic regimen that includes herbal teas, and he does stretching and ab workouts daily.
"We say, 'If it's not going to hurt, let's try it,'" says Hopkins, adding with a laugh, "No matter how much naturopathic cleansing I do, I'm always going to be full of crap!"
That sense of humor has proven vital, too.
"When he's having a moment, I have the strength to lift him," says Jennifer. "And when I'm having a moment, he has the strength to make me laugh. We cling to that."
Trying to keep life as normal as possible has been important to Hopkins and Jennifer, especially when they're at home with their three daughters, Sarah Grace, 13, and twins Lily Faith and Margaret Hope, 10.
"They're young, so they don't know the gravity of this disease yet, which is fine for us right now," says Jennifer, who decided with Hopkins to wait until after Christmas Day 2021 to tell the girls about what was going on.
While out playing volleyball in their neighborhood, Hopkins tripped on some broken pavement, and he used it as a segue to tell them that his balance was off because he has ALS.
"Grace asked, 'Could you die?' I said, 'Yes.' Faith said, 'Could you be in a wheelchair?' I said, 'Yes.' Hope started crying," Hopkins recalls. "They didn't quite understand it, and they still don't, really. But neither do we."
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For now, Hopkins hopes to continue doing what he does best: making music.
"One of the beautiful things about my condition, if God-willing it remains the way it is for a couple of years, is I have the energy and the presence to make a big impact," says Hopkins, who is currently working on his fourth Christmas record. "I'm ready to go. I can still play, I can still sing, I can still make records — and I want to do all that. I'm trying to record everything I can in the event that one day I might not be able to."
He's also found new joy in the everyday moments with Jennifer and their daughters.
"A math problem that your 10-year-old brings you can be just as exciting as a big vacation," he says. "I'm trying to remember that."
As he looks to the future, Hopkins hasn't lost faith.
"I'm ready to fight this disease," he says. "I want to show my girls what a warrior their dad is."
For all the details on John Driskell Hopkins' fight against ALS, pick up the latest issue of PEOPLE, on newsstands everywhere Friday.