A Chicago trial due to start on Monday will open a window onto two Pakistani terrorist organisations and the men who plotted the 2008 Mumbai attacks, amid fears it could further inflame regional tensions.
It comes amid a diplomatic crisis as Pakistan struggles to deflect suspicion of official complicity with terrorism after US commandos killed Osama bin Laden in an urban compound only 55 kilometers from Islamabad on May 2.
Chicago businessman Tahawwur Hussain Rana, 50, is charged with providing material support to terrorists by acting as a messenger and providing a cover for a key figure in the bloody 60-hour Mumbai siege in which 166 people died.
David Coleman Headley -- Rana's old friend from military school in Pakistan -- has been cooperating with prosecutors ever since his October 2009 arrest and will be a star witness at Rana's trial.
Jurors are also expected to hear a series of conversations between the two men secretly recorded by the FBI.
Headley formally admitted to 12 terrorism charges in March 2010 after prosecutors agreed not to seek the death penalty or to allow him to be extradited to either India, Pakistan or Denmark to face related charges.
The Washington-born son of a former Pakistani diplomat and American woman, Headley admitted to spending months scoping out sites for the Mumbai siege and plotting to kill a Danish cartoonist.
In a plot that reads like a movie thriller, Headley spent two years casing out Mumbai, even taking boat tours around the city's harbor to find landing sites for the attackers and befriending Bollywood stars as part of his cover.
He was so eager to kill a Danish cartoonist, who sparked outrage with cartoons depicting the Prophet Mohammed, that he began working seriously on that plot two months before the Mumbai attack.
Headley also had Bollywood and one of India's most sacred Hindu temples in his sights as he began plotting a second India attack during a March 2009 surveillance trip.
India and Washington blamed the Mumbai rampage on Pakistan's banned militant group Lashkar-e-Taiba (LeT).
The attacks stalled a fragile four-year peace process between the two nuclear-armed south Asian rivals which were only resumed in February.
Rana -- who holds Canadian citizenship -- insisted after his October 2009 arrest that he is a pacifist who was "duped" into letting his old friend use his immigration services company as a cover.
But in pre-trial motions, his lawyers proposed defending Rana's actions by arguing he believed Headley was working on behalf of the Pakistan's ISI spy service, not terrorists.
Headley testified to a grand jury that he had told Rana about "my meetings with Sajid and others in Lashkar" and "how I had been asked to perform espionage work for ISI," court records show.
"I explained to him that the immigration office would provide a cover story for why I was in Mumbai," Headley said, according to court records.
Judge Harry Leinenweber ruled against this proposed defense on legal grounds -- Rana is being prosecuted for his actions in the United States and even if Headley were acting on behalf of the ISI neither he nor Rana would be exempt from US laws.
However, the trial could nonetheless lend credence to suspicions that the ISI was involved in the attack because three of the conspirators named in the indictment are ISI officers, court records showed.
"This is going to be yet another brick in this very large wall of suspicion that we have about Pakistan," said Khalil Marrar, a political science professor at DePaul University who has been following the case.
None of the men are in US custody and a spokesman for the US attorney's office declined to say whether the US government would be seeking their extradition or even knows their whereabouts.
Headley -- who changed his name from Daood Gilani so he could hide his Pakistani heritage -- joined LeT in 2002, attending terrorist training camps five times over the next three years.
He began working with an al Qaeda-linked group in Pakistan called Harakat-ul-Jihad-Islami on the Danish plot after LeT became distracted with the final planning for the Mumbai attack, a plea agreement said.
Jury selection in Rana's begins on Monday. Opening statements are not expected until May 23.