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?
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.