Cryptic crossword clue
Route zero comes up through American state 4,4

The most common and most likely answer to this crossword clue is the 8 letter word MAINLINE

I've seen this crossword clue in The Daily Telegraph
M
A
I
N
L
I
N
E

Buddy explains!

The straight part
We know that "Route" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case route = mainline.
The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.
This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.

What does MAINLINE mean?

MAINLINE noun
  1. An airline's main operating unit, as opposed to codeshares or regional subsidiaries.
  2. The main repository for a software project, from which different versions (forks) may be split off.
MAINLINE verb
  1. To inject (a drug) directly into a vein.
  2. To integrate (code, etc.) into the main repository for a software project, rather than separate forks.
MAINLINE adjective
  1. Normal, principal or standard.
  2. Of or pertaining to the principal route or line of a railway.
  3. Of or pertaining to a surface railway as distinct from an underground, elevated or light rail one.

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