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Isaac Guerendo 2025 Fantasy Football Outlook: Elite Athlete, Elite Handcuff, Injury Worries
San Francisco 49ers running back Isaac Guerendo won't be the team's starter this season. That's no surprise, since RB Christian McCaffrey is still with the team. Given CMC's history with injuries, and the fact that Guerendo is now the team's clear RB2 after the departure of Jordan Mason to the Vikings, the former Louisville Cardinal immediately becomes one of the highest-upside running back handcuffs in the NFL. In limited action, Guerendo was an explosive play machine, ripping off huge runs, long receptions, and scoring touchdowns in his short 2025 season. Unfortunately, he suffered a litany of injuries, and is currently dealing with knee and ankle aliments. If you draft McCaffrey, you should make sure you take Guerendo as well. It's also a good idea if you want to keep him away from the CMC manager -- stashing Guerendo on your bench all season in leagues with enough bench spots is a good strategy. He has massive, week-winning upside every time he starts.
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