GOP Sen. Bill Cassidy faces Trump-backed challenger Julia Letlow in closely watched Louisiana primary 

President Donald Trump's grip on the GOP and the potential political fallout for his perceived enemies will face another test on Saturday in Louisiana's Republican primary.

Incumbent Sen. Bill Cassidy is competing against Trump-backed U.S. Rep. Julia Letlow (LA-5) and John Fleming, the state Treasurer and a former House Freedom Caucus Freedom member who served in multiple posts in the first Trump administration.

It's expected the threeway split could cause the race to go to a runoff next month if no candidate wins an outright majority in Saturday's primary.

Trump upended the race in late January when he encouraged Letlow to enter in hopes of defeating Cassidy, who in 2021 voted to convict the president in his second impeachment trial. She launched her campaign just days later.

Cassidy, asked by CNN on Friday why Trump wants him replaced, said, "I can't understand the president's mind."

He continued, "I'm not claiming the president loves me, no, but you can work with people even if you don't love each other if you got a common goal. And my goal is to make my country and my state and everybody who lives here better off."

Throughout the campaign, Cassidy has argued his record proves he delivers for Louisianans. The two-term senator has touted his work helping pass the HALT Fentanyl Act, negotiating the passage of the bipartisan Infrastructure Investment and Jobs Act and championing healthcare.

In 2024, Trump won the deep-red state with 60% of the vote, and if his preferred candidate wins, it would mark another victory for the president in his efforts to oust those he views as disloyal. Trump-backed candidates recently defeated several Indiana state senators who opposed his redistricting plans.

Cassidy could now be staring down the end of a long political career as part of a shrinking class of GOP lawmakers to have broken with the president. He is one of three remaining senators in the upper chamber to have voted to convict Trump.

Letlow has been anything but shy about Trump's endorsement, casting Cassidy as disloyal and Fleming as out of touch with the president. Her campaign messaging has focused in part on defending parental rights and securing the border.

The first Republican woman from Louisiana to be elected to Congress, Letlow romped to victory in 2021. She ran in a special election for the House after her husband, who was elected to the office, died from COVID-19-related complications before he could take office.

Cassidy's campaign has labeled her "Liberal Letlow" and unleashed a wave of attacks portraying her as a champion of DEI over comments she made in 2020 while working at the University of Louisiana at Monroe.

In a recent debate against Fleming, Letlow defended her position at the time, arguing "the left completely hijacked" DEI and she has "spent the last five years in Congress working against it."

Meanwhile Fleming, who argues he is the most conservative candidate, told ABC News some pressured him to drop his campaign.

Fleming said he was eventually able to reach Trump by phone and the president called him "fantastic."

However Trump's public endorsement of Letlow has not changed.

Despite their fraught relationship, Cassidy has, at times, supported Trump's agenda. Cassidy, a physician and longtime proponent of vaccines, grilled Health Secretary Robert F. Kennedy Jr. -- a vaccine skeptic -- during his confirmation hearing but cast the deciding vote to confirm his nomination out of committee.

Most recently, Trump blamed Cassidy, chairman of the Senate health committee, for the stalling of his surgeon general pick, Make America Healthy Again-aligned Casey Means.

The shift from open, nonpartisan primaries to a closed system also complicates Cassidy's road to victory. Registered and unaffiliated, or "No Party" voters, choose between the two parties. If no candidate receives a majority, the race will head to a runoff on June 27.

In Louisiana, Democrats slightly outnumber Republicans with roughly 1 million registered voters in each party, according to the Secretary of State office. There are more than 813,000 "No Party" voters.

Adding to the fire is Landry's move to postpone the House primaries in the nationwide redistricting battle -- even as absentee ballots had been returned -- while keeping the Senate race on May 16. Lawsuits have been filed in response and some, including Cassidy and Fleming, warn the move is leaving voters confused.

Fleming hedged on whether he would endorse an opponent should he lose the race, adding he takes issue with what he calls dishonest ads, particularly from those backing Letlow.

"We'll have to wait and see," he said.

Business owner Mark Spencer is also running in the GOP primary.

In the Democratic primary, Nick Albares, Gary Crockett and Jamie Davis are vying for the nomination to unseat Cassidy. The Cook Political Report rates the race as solid Republican in the Pelican State.

The polls are open from 7 a.m. to 8 p.m. CDT on May 16.