When Superman is a boy, Krypto is always around but never appears when Superman is adult.
What is the reason that Krypto no longer appears?
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There was no canonical tidy end, but he died in pre-Crisis Action Comics #583, via the Kryptonite Man:
This was a flashback/retcon, likely to address the lack[s] of closure. Assist to @KHW: "This version of Krypto (Earth-One), including all history and corresponding appearances, was erased from existence following the collapse of the Multiverse in the 1985-86 Crisis on Infinite Earths limited series and is now considered apocryphal." - from Krypto's Wikia article.