The All-Pro left tackle has been instrumental to the team’s success. Since 2021, the 49ers have been 20 games over .500 with Williams in the lineup but just 4-6 without him. His replacement, Jaylon Moore, will face his toughest test yet against the Rams’ formidable pass rush, led by Jared Verse.

“49ers ruled out LT Trent Williams (ankle) and S Malik Mustapha (chest, shoulder) for Thursday night’s game vs. the Rams. DE Nick Bosa (hip, oblique), RB Isaac Guerendo (foot) and LB Dre Greenlaw (Achilles) are listed as questionable.” via Adam Schefter on X, formerly Twitter.

Williams’ absence has been a significant factor in the team’s struggles. The offensive line has faced challenges in run blocking and pass protection. Moore’s performance will be critical as the 49ers aim to maintain their playoff hopes.

The 49ers may be without more than Trent Williams

On the defensive side, Bosa is listed as questionable but could make his return after missing the last three games. Bosa, who was a limited participant in Wednesday’s walk-through, could provide a much-needed boost to the pass rush. “Bosa would give the defensive line the shot in the arm they need to get after Matthew Stafford,” noted Schefter. However, easing him back into action on a rotational basis may be the team’s strategy.

Another key player is Linebacker Dre Greenlaw, who has been a full participant in practice and is trending toward playing. Known for his energy and leadership, Greenlaw’s potential return could lift the defense emotionally and strategically, even if he is limited to 20-25 snaps.

Rookie safety Malik Mustapha has been ruled out with a chest and shoulder injury, forcing Ji’Ayir Brown into the starting lineup. While Brown gave up a touchdown in coverage last week, head coach Kyle Shanahan expressed confidence in his ability to step up against the Rams.

Running back Isaac Guerendo is listed as questionable but remains the only healthy option capable of handling a significant workload. With Guerendo’s dual-threat capabilities in the run and pass game, his availability will be crucial for the 49ers’ offensive rhythm. Left guard Ben Bartch is also sidelined with a high ankle sprain, adding further strain to an offensive line already missing its cornerstone in Williams.

Thursday’s game presents a challenging test for the 49ers, with key injuries on both sides of the ball. While Williams’ absence will be difficult to overcome, potential returns from Bosa, Greenlaw, and Guerendo could provide the spark needed to stay competitive against a tough Rams team. As the season hangs in the balance, every player’s contribution will count.