Work with a large gem (4)
I believe the answer is:
opal
'gem' is the definition.
(opal is a kind of gem)
'work with a large' is the wordplay.
'work' becomes 'op' (abbreviation for opus**).
'with' says to put letters next to each other.
'large' becomes 'l'.
'op'+'a'+'l'='OPAL'
(Other definitions for opal that I've seen before include "Milky-white mineral" , "Mineral used as a gemstone, of hydrated silica" , "Translucent gemstone" , "Opaque mineral used a gemstone" , "Gem-stone with a milky quality" .)