Lothar, who was just 51, starred in major German-language films including "The White Ribbon", an atmospheric mystery set in rural Germany during the build-up to World War I.
Although her family's lawyer confirmed her death on Wednesday, no cause was released.
Hamburg-born Lothar acted in several major theatre productions before moving into cinema, where she won a Bundesfilmpreis for her debut performance in the 1983 film "Eisenhans."
She then starred in several films by Austrian director Michael Haneke, including "The Piano Teacher" "Funny Games" and "The Castle", as well as alongside Kate Winslet in "The Reader."
She specialised in playing vulnerable, damaged women who found hidden reserves of strength. The Austrian director Haneke frequently looked to her to embody characters pushed to the limit.
In "The White Ribbon", which won the Palme d'Or in Cannes in 2009, she played a midwife who submits to a humiliating loveless affair with the predatory town doctor.
In "Funny Games" she and her husband played a middle-class couple terrorised by two sadists during a home invasion.
And she appeared opposite Isabelle Huppert in Haneke's harrowing "The Piano Teacher" based on a play by Nobel laureate Elfriede Jelinek.
A celebrated character actor on stage as well as the screen, Lothar worked with some of Europe's most prominent theatre directors including Peter Zadek and Luc Bondy.
The Frankfurter Allgemeine Zeitung on Thursday called her an "actress of
"Theatre and film will no longer know in the future whom to entrust with the torn, courageous, endlessly fragile characters who live on the edge," Der Spiegel magazine wrote in its online edition.
Acclaimed German actor Ulrich Tukur, who appeared in several stage productions with her, told German radio that she had a "dark energy" which she knew to deploy to great effect in her performances.
"There was always a lot of desperation in what she did," he said.
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Born November 15, 1960 in the northern port city of Hamburg to actor parents, Lothar later moved to Berlin where she also enjoyed doing the occasional television crime show.
Her husband Ulrich Mühe died of cancer aged 54 in 2007, shortly after playing the lead role in the Stasi thriller "The Lives of Others."
The couple are survived by two children, Sophie Marie and Jakob.