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In Up Your Arsenal, the Ion Cannon was part of the planetary defense system on Koros. Clank hacked into it, and used it to destroy the first Biobliterator. It was named Nefarious's BFG.

In Deadlocked, Ratchet could use The Harbinger to call down a strike from a horde of orbital Ion Cannons.

In A Crack in Time., Azimuth used his ship's Ion Cannons, to help Ratchet defeat the VX-99 in Axiom City. It was used to destroy the VX-99's outer domes.

While the actual Ion Cannon did not make an appearance in Into the Nexus, a turret was used to duplicate it's role in destroying the Biobliterator in the Intergalactic Museum of History.