Lowe, who has starred in hit US political drama the 'The West Wing' and is currently starring alongside Sally Field and Calista Flockhart in Channel 4 drama 'Brothers & Sisters', follows in the footsteps of US rapper Snoop Dogg, who starred in the last spot in January.
In the ad, created by Mother, Lowe is shown pitching to long-term characters Dresden and his assistant Elliot in sunny Los Angeles, with a swimming pool in the background.
While Lowe tries to make his pitch, suggesting that he could play the Robert Redford role in the remake, Dresden interrupts to say "hasn't he got the most incredible blue eyes".
Dresden then goes on to suggest that instead of 'Watergate' they could create a film involving water with Lowe playing the part of a lifeguard who brings down a corrupt coastguard using video calling to "Deep Throat on an Orange mobile phone".
As Lowe attempts to point out why this would be ridiculous, Dresden pulls out skimpy swimming trunks with the Orange logo on and flings them at the actor.
The spot ends with Lowe becoming so frustrated that he threatens to strangle Dresden to which he replies "As long as you look at me while you strangle me I'd be fine with that."
Rachel Macbeth, head of advertising and design, Orange UK said: "We are so excited about this new addition to the Orange Film Funding Board ad series. Watching Rob Lowe arguing with the Orange Film Board set against the Malibu coastline is truly an entertaining sight. Rob is a welcome addition to the ever popular ad series and we feel we have raised the bar with this ad."
The long-running Orange Gold Spot series has including starring roles from Macauley Culkin as a death row prisoner, Mena Suvari as Joan of Arc, Val Kilmer in the Wild West and Darth Vader.
The Rob Lowe spot breaks in cinemas from May 16.
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