INDIANAPOLIS — They always will be joined at the hip.

Think of Peyton Manning and Ryan Leaf. Or Drew Bledsoe and Rick Mirer.

If positions don’t matter to you, think of Edgerrin James and Ricky Williams.

It’s the nature of the NFL beast that high-profile players enter the league as lottery picks, then spend the early portion of their careers measuring up, trying to measure up or being criticized because they don’t measure up with their high-pick peers.

That’s a storyline whose first chapter begins Sunday at Houston’s NRG Stadium.

Anthony Richardson vs. C.J. Stroud.

Richardson, selected No. 4 overall in the April draft by the Indianapolis Colts, and Stroud, taken No. 2 overall by the Texans.

Neither of the longtime friends will step on the field at the same time, other than to share hugs and small talk prior to the game and congratulate or console afterwards.

But trust us, everyone’s attention will be focused on Richardson vs. Stroud, Round 1.

Well, not everyone.

“It’s not quarterback versus quarterback,’’ argued Shane Steichen. “It’s the Houston Texans versus the Colts. That’s what we’ve got to focus on and treat it that way.’’

Yet, there’s no denying the intriguing subplot. Not just Sunday, but for the foreseeable future. If the Colts and Texans were right on draft day, Richardson vs. Stroud will be must-see viewing for the next eight, 10, 12 seasons.

On a larger scale, the future of the AFC South could rest in young, exciting hands. Jacksonville hitched its destiny to Trevor Lawrence with the No. 1 overall pick in 2021, and the Tennessee Titans got their heir apparent to Ryan Tannehill in Will Levis with the second pick in round 2 in April (No. 33 overall).

But back to Richardson vs. Stroud.

Zaire Franklin has a full plate as a Colts’ defensive captain. He set a franchise record with 166 tackles last season and piled up 18 in the opening loss to Jacksonville — a career-high and tied for the third-most in team history.

He prides himself in keeping abreast with whatever narrative is floating around the NFL landscape.

Richardson vs. Stroud?

“I’m the type of person that likes to think about stuff like that,’’ Franklin said. “It is cool.’’

Franklin didn’t hesitate to approach Richardson and make certain he understood the short and long-term hype that followed him into the NFL. It took firm root April 27 when the Carolina Panthers selected Bryce Young No. 1, followed by Stroud and Richardson.

Franklin, though, took a slightly novel approach.

“I talked to him when he first got here and told him, ‘Obviously, you’re going to be compared with Bryce and C.J. your whole career no matter what. But at the end of the day, those aren’t the guys you’re competing against. You’re competing against Pat (Mahomes). You’re competing against Josh Allen. You’re competing against the big dogs.’

“I feel like Anthony’s got that mentality where he’s just going to focus on himself and just keep worrying about getting better and that’s all you can do. But you can’t help but (realize) who you’re going to be compared with.’’

Sunday, Richardson will be compared with Stroud.

In week 9, everyone will wonder how he stacks up against Young.

Naturally, there’s historical perspective to consider, now and later:

*Sunday marks just the seventh time since 1950 top-4 quarterbacks have faced each other as rookie starters.

If you’re interested, the previous six: Lawrence and the Jets’ Zach Wilson (No. 2 overall) in 2021; Tampa Bay’s Jameis Wilson (1) and Tennessee’s Marcus Mariota (2) in 2015; Cleveland’s Tim Couch (1) and Cincinnati’s Akili Smith (3) in ’99; Manning (1) and San Diego’s Leaf (2) in ’98; New England’s Bledsoe (1) and Seattle’s Mirer (2) in ’93; and New England’s Jim Plunkett (1) and Houston’s Dan Pastorini (3) in ’71.

*the Manning-led Colts edged the Leaf-led Chargers, 17-12, in week 5 for the first of Manning’s 186 career regular-season wins.

*Sunday is just the second time quarterbacks under the age of 22 have started against each other. The only other tandem: Winston and Mariota.

*Richardson and Young have a week 9 meeting in Carolina, and of course, there’s Richardson’s week 18 rematch with Stroud.

Richardson and Stroud share a relationship that stretches back to high school; Richardson at Eastside in Gainesville, Florida, and Stroud at California’s Rancho Cucamonga.

“Yeah, ‘Ant’ is my guy, man,’’ Stroud told Texans media this week. “Known him since high school. Competed against each other at Elite 11 and became real good friends there and kind of kept a relationship when he was at Florida and I was at Ohio State.

“Really, really happy for him. He’s always been a hell of a player to me, and I’m just really excited to see what he does in his career. I’m always going to be supportive of him and be a brother and a friend to him … I’m rooting for him, and I hope that everything in his career goes well except for when he plays the Texans.

“I love him to death.’’

Ditto, Richardson.

“I love C.J.,’’ he said. “I’ve known him since high school. We went to a few camps together, been through college together, talk a lot.

“So, whenever I see him, I always tell him he’s a GOAT. He’s a baller. I’m looking forward to playing against him and against their team. But yeah, he’s definitely a dog. He’s a baller.’’

It’s unlikely the high-profile meeting/stage will prove too large for Richardson. He can draw from a similar experience last year at Florida. After posting a breakout game with a 29-26 upset at No. 7 Utah in the season-opener — 168 passing yards, 106 rushing yards and three TDs — Richardson moved on to a week 2 meeting with Kentucky. He was driven to win his one-on-one “matchup’’ with Levis, who already was projected as a first-round pick.

Richardson failed to deliver: 14-of-35 passing for 143 yards and an interception returned for a touchdown, and 12 yards on six carries. Kentucky rolled, 26-16.

“The last time I tried to compete with somebody else,’’ he said, “I didn’t play great. I’m just focused on myself, focused on my details and trying to help my teammates.’’

Each rookie is searching for his early signature moment.

Richardson was the youngest starting quarterback in Colts’ history and the franchise’s first rookie to rush and pass for a touchdown in his first game. His completion percentage (64.9) and completions (23) are club records by a rookie QB in his first start, and he led the team in rushing with 40 yards on 10 carries.

Yet the Colts lost to Jacksonville, 31-21.

Stroud passed for 242 yards, completed 63.6% of his passes and didn’t suffer an interception. He rushed four times for 20 yards.

Yet, the Texans were limited to three Ka’imi Fairbairn field goals in their opening 25-9 loss at Baltimore.

Steichen and Houston’s first-year head coach DeMeco Ryans have just one regular-season video and snippets from preseason and college games to prepare for each team’s quarterback of the future.

Even so, they know what’s coming.

Steichen on Stroud: “He gets the ball out of his hands quick. He makes quick decisions. He’s a pure passer. He can spin it.’’

Ryans on Richardson: “As I watched him in the pre-draft process, you saw a very talented young kid. Man, he was a playmaker … big-time playmaker. Made a lot of explosive plays at Florida.

“You also saw a kid that also has a lot of room to improve and you’ve seen that growth over his tape now, being with the Colts. He has the talent to play in this league. That’s the one thing you want to see and he has it and he has dynamic playmaking ability.’’