Australia's most prominent Indigenous music artist Dr G Yunupingu has died aged 46 and is being mourned by family and friends as a "genius and wonderful human being".

The singer — from the remote community of Galiwin'ku on Elcho Island, 500 kilometres east of Darwin — shot to stardom in 2008, winning an ARIA Award for his namesake album.

The album hit triple platinum in Australia, silver in the UK and charted in multiple countries worldwide.

Dr Yunupingu's record label Skinnyfish described him as "one of the most important figures in Australian music history, blind from birth and emerging from the remote Galiwin'ku community ... to sell over half a million copies of his albums across the world, singing in his native Yolngu language".

His friend Vaughan Williams told the ABC the artist had been staying in Darwin.

Mr Williams said he was contacted by people concerned that the singer — who had contracted Hepatitis B as a child, causing liver and kidney disease — had not recently accessed renal treatment.

He said he took the singer to Royal Darwin Hospital on Thursday, and was informed about the death on Tuesday afternoon.

Mr Williams had known the singer since he was 15.

"He was a shy, humble and wonderful young man, who turned out to have such a fantastic voice," he said.

"He was a musical genius who could do rock, gospel, soul. He could do it all."

Yunupingu's death a 'deafening silence'

Yorta Yorta soprano and Dean of Indigenous performance at the Victorian College of the Arts, Deborah Cheetham, said Dr Yunupingu's music changed the landscape for Indigenous artists.

"[Dr Yunupingu and his record label] ignited a fire, for Aboriginal Australians, that singing in language is so meaningful, for us, a way of connecting with who we are, where we come from," she said.

"Today the celebration of song in language is something that's become the fabric of society.

"He changed that world for us."

Ms Cheetham said it was difficult for many to accept Dr Yunupingu had died so young.

"I'll tell you what, when a voice like that is silenced in the world it's a kind of deafening silence that takes some time to get used to," she said.

'His legacy will continue'

Dr Yunupingu, a Yolngu man from the Gumatj clan, had his first guitar by the age of six, which he learned to play upside down because he was left handed.

In his mid-teens he joined the band Yothu Yindi under the guidance of lead singer Mr Yunupingu.

He later went on to play with the Saltwater Band, before being persuaded by friend Michael Hohnen to go solo.

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The singer played with Sting in Paris, and performed for former US president Barack Obama, Crown Prince Frederik and Princess Mary of Denmark.

In 2011 he became seriously ill and returned to Elcho Island, but he then travelled to perform at the Queen's diamond jubilee concert in London in 2012.

After that performance he had to return home and cancel the European tour that was to have followed it.

Skinnyfish said he gave back to his community as the driving force behind the G Yunupingu Foundation.

"He created opportunities for young people across the Northern Territory," the record label said.

"His legacy as a musician and community leader will continue as his life's work continues its positive impact on Elcho Island, the Northern Territory, Australia and the world."

Mr Williams said he was particularly devastated because he felt his friend's death was "preventable".

"Questions need to be asked about how this could happen. It's a failure of all of us that we have lost such an amazing human being," he said.

"I feel he was trapped in the same cycle of bad health that so many Indigenous people are trapped in."

The family has requested that Dr G Yunupingu's image not be published.