The 'Hump De Bump' hitmakers reconvened earlier this year after a two-year hiatus, which allowed the rockers to concentrate on their individual side-projects. Despite tentative talk of a new album, the band have been dogged by rumours that they are on the verge of splitting.
Frusciante, who has so far released ten of his own LPs, used the group's break to work on his latest record The Empyrean, which was made available at the start of the year.
However, Music Radar now claims that the 39-year-old has quit the band to continue work on his own material. He is said to have already been replaced by Josh Klinghoffer, who toured with the Red Hot Chili Peppers in 2007 and has previously played for Gnarls Barkley and PJ Harvey.
A source said: "Josh Klinghoffer has been playing with the group for a couple of months now. Optimistically, the Peppers are trying to lock down a replacement for John, who has apparently quit.
"Mentally, John checked out a long time ago. He's interested in doing his own thing, his own albums - the whole big rock band machinery just doesn't appeal to him anymore."