Jimmy Garoppolo couldn't have a tougher assignment in his first NFL start. While Tom Brady is suspended, the third-year quarterback faces the Arizona Cardinals, one of the Super Bowl favorites, a team owning a strong defense.
In prime time.
''There's so much going on right now,'' Garoppolo said. ''Mentally, I'm straight Arizona, but it is a phenomenal opportunity. This is why you play the game. You play to be in the game and play; you don't want to be the backup. The opportunity is here. I've just got to go take advantage of it.''
That opportunity is thanks to the ''Deflategate'' saga that finally has played out. Brady is gone for four weeks, and Jimmy G is the guy.
''I think that just comes with being a quarterback,'' said of taking ownership of the position - for now.
''Naturally, that kind of happens on its own. But yeah, you want to go in there and let the guys know that you're here to work and here to do your job the right way.''
Arizona is quite the challenge, with perhaps the most talented roster in the NFL. And back from injury is All-Pro safety Tyrann Mathieu, who adds spark and gumption to the defense.
How did coach Bruce Arians know the Honey Badger was ready after the safety missed the preseason?
''It's about two interceptions every day,'' Arians said. ''He flies around and makes every check and has the energy and passion that he always has.''
Also Sunday, it's Green Bay at Jacksonville, the New York Giants at Dallas, Minnesota at Tennessee, Miami at Seattle, San Diego at Kansas City, Oakland at New Orleans, Cincinnati at the New York Jets, Buffalo at Baltimore, Cleveland at Philadelphia, Chicago at Houston, Tampa Bay at Atlanta, and Detroit at Indianapolis.
On Monday night, the doubleheader has Pittsburgh at Washington and the Rams - yes, representing Los Angeles - at San Francisco.
The season kicked off Thursday night with Denver's 21-20 victory over Carolina in a rematch of the Broncos' Super Bowl victory. Carolina's Graham Gano missed a 50-yard field goal with four seconds remaining.
Green Bay at Jacksonville
''I'm playing football,'' Packers receiver Jordy Nelson said when asked if his knees were an issue as he comes off a torn right ACL in a preseason game last summer at Pittsburgh.
Nelson's availability is a key for Green Bay, which ranked only 25th in passing a year ago despite having Aaron Rodgers.
If the Jaguars' rebuild is nearing completion, these are the kind of games they need to win. Or at the very least, be competitive.
New York Giants at Dallas
Time to find out if all that optimism coming out of Dallas about Dak Prescott stepping in for injured quarterback Tony Romo is valid.
''Wouldn't have expected for it to happen this early, but it did unfortunately,'' Prescott said. ''For it to be a reality now, to be a starting quarterback, it's fun just to get in the huddle and be around a bunch of great guys and get to play in this division.''
It's also time to find out if all those defensive changes the Giants made - Olivier Vernon, Damon Harrison, Janoris Jenkins, Eli Apple - warrant any enthusiasm for them and new coach Ben McAdoo.
Minnesota at Tennessee
Minnesota is another team without its starting QB - Teddy Bridgewater wrecked his left knee in practice and is gone for the season. The Vikings dealt for Sam Bradford this week, but how soon he will be ready is a huge unknown.
No such issues for the Titans with Marcus Mariota. How their running game with newcomers DeMarco Murray and Derrick Henry performs against Minnesota's stout defense could be telling.
Pittsburgh at Washington, Monday night
Without Le'Veon Bell in the backfield and Martavis Bryant at receiver (both suspended), the Steelers would appear undermanned. They still have Ben Roethlisberger throwing to Antonio Brown, though, and veteran DeAngelo Williams was a terrific stand-in last year for Bell.
The Redskins added All-Pro Josh Norman at cornerback to bolster a D that ranked 25th against the pass. They also need to figure out their running game.
Miami at Seattle
Adam Gase made his reputation as a QB guru while working with Peyton Manning in Denver. He now is in charge of the Dolphins, and Ryan Tannehill is no Manning.
Even worse, the Seahawks seem to be on a mission, with a nasty defense, productive offense and everything in place for another Super Bowl run - if their offensive line coalesces.
San Diego at Kansas City
How predictable was this: Chargers top draft pick Joey Bosa has a damaged leg after missing all of preseason in a holdout. The defensive end likely won't suit up.
Kansas City also will be minus some key players, including star linebacker Justin Houston and running back Jamaal Charles. Coach Andy Reid said it's ''a stretch'' to expect Charles to suit up.
Oakland at New Orleans
Drew Brees reworked his contract. Now if only the Saints can rework a defense that ranked 31st across the board on the yardage charts in 2015. The hope in the Big Easy is that linebacker James Laurinaitis can spark an already banged-up unit.
Like Jacksonville, Oakland is looked at as a rising team. It has one of the league's best defensive players in Khalil Mack, and the offense should be balanced. Can the secondary slow Brees?
Cincinnati at the New York Jets
The first game in a very tough opening stretch for the Jets, who face five 2015 playoff clubs in six weeks. Their front line on D is as good as any in football, but their O-line is questionable. Adding Matt Forte to the backfield should help in the short term.
Cincinnati has never won in the Meadowlands: 0-9 vs. the Jets, 0-3 vs. the Giants. The defense is formidable, too, and QB Andy Dalton is back healthy. He will be without dangerous TE Tyler Eifert.
Buffalo at Baltimore
Troubled Buffalo has been hit by suspensions and injuries already.
''We don't want to major in putting hurdles out there,'' coach Rex Ryan said during training camp. ''But we seem to be doing a pretty good job of it right now.''
The Ravens' 2015 was ruined by injuries, and most of the key players who were sidelined - Joe Flacco, Terrell Suggs, Justin Forsett, Steve Smith - are ready.
Los Angeles at San Francisco, Monday night
Los Angeles is back in the NFL for the first time since 1994, though the Rams don't play at home until next week. Top overall draftee Jared Goff is the backup quarterback to Case Keenum for now.
Seemingly the focal point for most people watching the 49ers is Colin Kaepernick not standing for the national anthem. Whether he does or not, Chip Kelly debuts as San Francisco's coach.
Cleveland at Philadelphia
While Goff sits, the guy taken after him in April, Carson Wentz was handed the Eagles' job behind center. Wentz hasn't played since the preseason opener when he broke some ribs.
The Browns brought in Robert Griffin III, hoping he can resurrect his QB career after it fell apart in Washington. New coach Hue Jackson works well with the position.
Chicago at Houston
Three-time Defensive Player of the Year J.J. Watt comes off two offseason procedures on his back. Not having him at full strength could undermine Houston's defense of the AFC South title, but Watt expects to play - and play well - on Sunday.
With Matt Forte gone, it will be intriguing to see what the Bears' running game looks like.
Tampa Bay at Atlanta
Some have pegged the Bucs as a rising team, and they have the offense to be dangerous behind Jameis Winston, Doug Martin and Mike Evans. Is their pass rush upgraded enough.
Atlanta looked dynamic in going 5-0 and 6-2 before fading to 8-8. Although coach Dan Quinn has a solid defensive background, the Falcons were last with 19 sacks in 2015 and must improve that - immediately.
Detroit at Indianapolis
The Lions have one victory in Indianapolis. In 1991. But their coach, Jim Caldwell, led the Colts to the Super Bowl in 2009. Longtime standout WR Calvin Johnson has retired, a Megatron-size hole Detroit must fill.
Colts QB Andrew Luck is expected to make his first regular-season start since Nov. 8, when his injury-ravaged season ended.
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