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The T.C.R.I. building is seen briefly in the fourth episode.
In "TCRI", the Turtles discover that T.C.R.I. is the Kraang's main headquarters on Earth, and April O'Neil finds blueprints of the main building in Brooklyn. The bottom two thirds of it are ordinary offices where normal humans work, but the top third appears blank on the blueprints. The Turtles determine that this must be where the Kraang are hiding the portal to Dimension X and resolve to shut it down. With the help of April and Leatherhead, the Turtles break into the building but are captured by the Kraang. By the time they free themselves, the Kraang have already activated the portal and the monstrous Rock Soldier Traag comes through. The Turtles are no match for Traag, but Leatherhead comes to their aid and pulls himself and the alien back through the portal. With Leatherhead gone and the Kraang surrounding them the Turtles are forced to escape, leaving the portal operational since their bombs couldn't destroy it.
In Showdown, Part 1, Donatello and April learn through the Kraang Communication Orb (which April scavenged previously in Operation: Break Out) that the Kraang were planning an invasion by sending the Technodrome through the portal at T.C.R.I. The turtles launch a major mission to infiltrate T.C.R.I., using the Shellraiser and Metalhead as a diversion in the building's lobby as the turtles use their new Turtle Gliders to fly directly to the Kraang portal facility near the top of the building. The initial plan is to sneak in stealthily and use a Microfission Omni-Disintegrator gun to destroy the portal in a single shot, but this fails because the portal is unexpectedly protected by a force field, and in the process the turtles are discovered and lose the element of surprise. In a backup plan, Donnie hacks into the Kraang computer to disable the force field while his brothers keep the Kraang distracted; the force field comes down, but their gun has run out of power. Ultimately, their plan to stop the arrival of the Technodrome fails, and it comes through the portal over the T.C.R.I. building and starts flying over New York City. Though they can no longer prevent this, in a final desperate improvised plan, Leonardo orders his brothers to evacuate, and he destroys the Power Cell with his own katana, causing it and the entire facility to explode, destroying the portal and wrecking T.C.R.I. Leo barely jumps through the glass to avoid the explosion, but ends up free falling down the side of the building, only escaping death when Raphael catches him with his Turtle Glider.
In Mikey Gets Shellacne, Michelangelo contracts potentially deadly turtle zits from a reckless application of a reject batch of Retro-Mutagen on his own skin. Donatello can treat this condition, but needs a rare molecular centrifuge, recalling that he once saw such a centrifuge at T.C.R.I. before the facility was destroyed. The turtles go to the ruins of T.C.R.I.'s top floors to scavenge for a centrifuge, only to find that Baxter Stockman is also scavenging T.C.R.I. at the same time, and has already found the centrifuge. Stockman fends off the turtles with his M.O.U.S.E.R.S.. During the fight, Dogpound unexpectedly enters, having tracked down Stockman to force him to develop a Retro-Mutagen to reverse Dogpound's mutation. Dogpound captures Stockman and further wrecks part of the T.C.R.I. facility to prevent the turtles from pursuing his escape.
In The Kraang Conspiracy, it is revealed that the Kraang have reclaimed and rebuilt their facility at T.C.R.I.