Jo Johnson, younger brother of Prime Minister Boris Johnson, is quitting as an MP and minister, saying he is "torn between family loyalty and the national interest".
The business minister and Tory MP for Orpington tweeted that there was an "unresolvable tension" in his role.
Mr Johnson voted Remain in the 2016 EU membership referendum, while his brother co-led the Leave campaign.
He resigned as a minister last year in protest at Theresa May's Brexit deal.
But he re-entered government during the summer, after Conservative Party members elected his brother as leader.