Run down irregular gradient beginning to exhaust (9)
I believe the answer is:
denigrate
'run down' is the definition.
(I've seen this before)
'irregular gradient beginning to exhaust' is the wordplay.
'irregular' indicates anagramming the letters.
'beginning to' indicates taking the first letters.
The first letter of 'exhaust' is 'e'.
'gradient' with letters rearranged gives 'denigrat'.
'denigrat'+'e'='DENIGRATE'
(Other definitions for denigrate that I've seen before include "Criticise, belittle" , "Slight" , "Blacken" , "Run down" , "Bad-mouth" .)