Colts quarterback Anthony Richardson appears to have suffered his second significant injury in five NFL games.

The No. 4 overall selection in the 2023 draft was officially ruled out after leaving Sunday’s game against the Titans in the second quarter with a right shoulder injury.

The 21-year-old Richardson had missed the Colts’ Week 3 game against the Ravens with a concussion.

Backup quarterback Gardner Minshew filled in for Richardson in that game and led the Colts to a 22-19 overtime victory.

He also replaced the rookie late in Sunday’s first half after Richardson landed on his right shoulder after being tackled by Tennessee linebacker Harold Landry on a four-yard scramble.

The former Florida star completed nine of 12 passes for 98 yards before departing and picked up an additional five yards on the ground.

Minshew went 11-for-14 passing for 155 yards.

The Colts went on to win 23-16 to improve to 3-2.