If a creature with protection from red is targeted by a red spell, does the spell fizzle?

Protection from a quality (like red) grants four specific shields, often remembered as DEBT: the protected permanent cannot be Damaged, Enchanted/Equipped, Blocked, or Targeted by sources of that quality (CR 702.16b). The targeting restriction is the key one here.

When a red spell is cast and targets a creature with protection from red, the target is technically legal at the time of casting — protection does not prevent a spell from being cast targeting the creature. However, when the spell tries to resolve, the game checks whether all targets are still legal (CR 608.2b). Because the creature has protection from red, it is an illegal target for that red spell at resolution.

If all targets of a spell are illegal at resolution, the spell is countered by the game rules and put into the graveyard without any effect (CR 608.2b). This is commonly called "fizzling." If a spell had multiple targets and only some became illegal, it would still resolve but would not affect the illegal targets.

Example: Your opponent controls a White Knight (which has protection from black). You cast Lightning Bolt (a red instant) targeting it. When Lightning Bolt tries to resolve, White Knight's protection from red makes it an illegal target, so Lightning Bolt is countered by the game rules, goes to the graveyard, and the Knight takes no damage.

Note: If protection is granted after the spell has already resolved its targeting check (which doesn't happen mid-resolution normally), the same rule applies — the protection must simply be present at the time of resolution to cause the spell to be countered.