David Arquette found referring to Alexis Arquette as his sister one of the "hardest parts" of her transition.
The 'Scream' actor's sibling transitioned from male to female - changing her name from Robert - in 2007 so he can identify with what the Kardashian-Jenner family are going through with patriarch Bruce Jenner's decision to undergo gender reassignment and hopes he is "comfortable" with his decision.
Asked about Bruce's situation, David said: "It's such a personal thing, especially being in the spotlight. It must be really difficult for everyone.
"He seems like a really sweet guy, girl... To be honest with you, that little faux pas that happened, is one of the hardest parts, to call my brother my sister now... but whatever makes them comfortable."
The 43-year-old actor says he learned to "just grow and accept" his sister's situation.
He added to 'Access Hollywood': "It's family, you deal with all kinds of stuff."
David - who has 10-year-old daughter Coco with ex-wife Courteney Cox and 11-month-old son Charlie West with new wife Christina McLarty - welcomes the way society's attitude to the transgender community is changing.
He said: "I like the new age of our society, where we're more accepting and understanding of diversity and it just makes our world more colourful. As long as you're not a terrible person, hurting people, more power to you."