The international trade secretary has said the British government's first focus is to maintain peace in Northern Ireland after the US warned a trade deal with the UK is at risk if Westminster changes the protocol.
US House Speaker Nancy Pelosi said altering the protocol could damage the Good Friday Agreement, which aims to help maintain peace between Northern Ireland's communities.
The UK's international trade secretary, Anne-Marie Trevelyan, dismissed the warning as she said: "We have a £200bn trade relationship (with the US) that goes on day by day with all our businesses and that is fantastic.
"But the British government's focus will always, first of all, be the sovereignty of the UK and ensuring the Good Friday Agreement can work as it was intended, to ensure peace and prosperity on the island of Ireland."
She added that she was looking forward to discussing the issue with the Americans, who she admitted played a "very important part of bringing the Good Friday Agreement into being".
But, Ms Trevelyan said: "What I want to make sure is if there are those that don't understand what it is that we are doing, we are very happy and will continue to discuss with all those whose commitment is to the Good Friday Agreement being a stable and long term insurance of peace and prosperity and stability on the island of Ireland."
The UK's Northern Ireland minister, Conor Burns, earlier said there can be "no connection" between the trade deal and "doing the right thing" for Northern Ireland.
Earlier this week, British Foreign Secretary Liz Truss said ministers plan to introduce legislation to change the protocol - which governs Northern Ireland's post-Brexit trade arrangements - in the coming weeks.
She said she would prefer negotiations with the EU, but would implement the changes if that cannot happen.
The protocol averts the return of a hard border with the Republic of Ireland but has resulted in a new border in the Irish Sea as some goods coming from the rest of the UK are subject to customs checks.
Some companies have ceased sending goods to Northern Ireland because of the extra cost and paperwork - something Ms Truss wants to change.
In a statement, Ms Pelosi said: "It is deeply concerning that the United Kingdom is now seeking to unilaterally discard the Northern Ireland Protocol.
"Negotiated agreements like the Protocol preserve the important progress and stability forged by the Good Friday Accords, which continue to enjoy strong bipartisan and bicameral support in the United States Congress."
She said she has told Boris Johnson, Ms Truss and MPs before that "if the United Kingdom chooses to undermine the Good Friday Accords, the Congress cannot and will not support a bilateral free trade agreement with the United Kingdom".
She urged "constructive, collaborative and good-faith negotiations to implement an agreement that upholds peace".
Conor Burns reacted to her comments by saying the government's "absolute priority" is "protecting the Belfast/Good Friday Agreement and the institutions that spring from it".
"As Nancy Pelosi knows we seek an ambitious FTA [free trade agreement] with the US," he tweeted.
"But there can be no connection between that and doing the right thing for NI. None."
There is currently no sitting Northern Ireland Assembly because the DUP is refusing to take part in mandatory power-sharing unless the protocol is altered or scrapped.
DUP leader Sir Jeffrey Donaldson said Ms Pelosi "needs to recognise it is the protocol that is harming and undermining the agreement and that is why we need to deal with it".
The EU has said it will not be adjusting its mandate to be able to change the protocol.
A trade deal with the US has proved more difficult than first hoped, with Northern Ireland becoming a sticking point.
In September last year, President Joe Biden - who is proud of his Irish roots - told Sky News he feels "very strongly" he does not want a change to the "Irish accords" as the end result would be having a "closed border in Ireland".
On a trade deal, Mr Johnson admitted at the time: "I have plenty of reason to be optimistic about that. But the Americans do negotiate very hard."