If the system doesn't protect him he's left exposed and his lack of intelligent as a defender is obvious to see. He's physically dominant and is good on the ball but he doesn't read the game very well and doesn't anticipate the way you expect a 30-35m defender to do.
I used to watch him at Sampdoria and didn't think he was that good and at Valencia I always felt like he looked a bit too prone to lapses in concentration and couldn't always anticipate too well.
Under a different manager he'd be a resounding success but when your manager doesn't respect defensive organisation it will just make Mustafi look like a donkey every now and then.
Look at David Luiz if you want to see the kind of system you need Mustafi in to truly bring out the best in him.