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Klepfisz was born in the Warsaw Ghetto on April 17, 1941, the daughter of Michał Klepfisz, a member of the Jewish Labour Bund (Yiddish: der algemeyner yidisher arbeter bund), and his wife, Rose Klepfisz (née Shoshana Perczykow; 1914-2016). In late April 1943, when she had just turned two years old, her father, was killed, on the second day of the Warsaw Ghetto Uprising (Yiddish: varshever geto oyfshtand).
Earlier in 1943, Klepfisz's father had smuggled Irena and her mother out of the ghetto; Irena was placed in a Catholic orphanage, while her mother, using false papers, worked as a maid for a Polish family. After the uprising, her mother retrieved her from the orphanage and fled with her into the Polish countryside, where they survived the Second World War by hiding and concealing their Jewish identities, aided by Polish peasants. After the war, the remaining family moved briefly to Łódź before moving to Sweden in 1946. Irena and her mother immigrated to the United States in 1949.
Klepfisz attended City College of New York, and studied with distinguished Yiddish linguist Max Weinreich, a founder of the YIVO Institute for Jewish Research. Klepfisz graduated CCNY with honors in English and Yiddish.
Today Klepfisz is known as a Yiddishist, but her מאַמע־לשון (mame-loshn, literally "mother tongue") was Polish; as a child she also learned Swedish. She began to learn Yiddish in Łódź in elementary school after the Second World War. She learned English after emigrating to the United States. In The Tribe of Dina: A Jewish Women's Anthology, which she co-edited with Melanie Kaye/Kantrowitz, Klepfisz describes the experience, up to age 16 or 17, of having "no language in which I was completely rooted".
Klepfisz has worked as an activist in feminist, lesbian, and secular Jewish communities. She is also co-founder of The Jewish Women's Committee to End the Occupation of the West Bank and Gaza (JWCEO). Along with Nancy Bereano, Evelyn T. Beck, Bernice Mennis, Adrienne Rich, and Melanie Kaye/Kantrowitz, Irena Klepfisz was a member of Di Vilde Chayes (English: The Wild Beasts), a Jewish feminist group that examined and responded to political issues in the Middle East, as well as antisemitism.
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Klepfisz began publishing her poems in 1971. She was a founding editor of Conditions, a feminist magazine emphasizing the writing of lesbians, and also was a co-editor of The Tribe of Dina: A Jewish Women's Anthology (the other co-editor was Melanie Kaye/Kantrowitz). Klepfisz has also been a contributor to the Jewish feminist magazine Bridges, and wrote the introduction to Found Treasures: Stories by Yiddish Women Writers.
She also authored an essay collection, Dreams of an Insomniac: Jewish Feminist Essays, Speeches and Diatribes, published by The Eighth Mountain Press  She is the author of "A Few Words in the Mother Tongue: Poems Selected and New" (with an introduction by Adrienne Rich) published by The Eighth Mountain Press, which was nominated for a Lamda Prize in Poetry in 1990. <Women's Review of Books  f></ref>
- "Irena Klepfisz" [author biography]. In: Jewish American Literature: A Norton Anthology. New York: W. W. Norton & Company, 2001. Edited by Jules Chametzky, et al. ISBN 0-393-04809-8. p. 1081.
- Kutzik, Jordan (April 15, 2016). "Remembering Archivist and Warsaw Ghetto Survivor Rose Klepfisz". The Forward. Retrieved 2016-07-05.
- Peterson, Nancy J. Against Amnesia: Contemporary Women Writers and the Crises of Historical Memory. Philadelphia: University of Pennsylvania Press, 2001. ISBN 0-8122-3594-0. p. 113–114.
- Klepfisz, Irena. "Secular Jewish Identity: Yidishkayt in America", The Tribe of Dina: A Jewish Women's Anthology, Sinister Wisdom Issue 29/30, p. 31.
- "Irena Klepfisz". Dartmouth College. Archived from the original on July 13, 2009. Retrieved 2013-11-02.
- Klepfisz author bio, The Tribe of Dina: A Jewish Women's Anthology, Sinister Wisdom Issue 29/30, p. 324.
- Klepfisz, Irena. "Secular Jewish Identity: Yidishkayt in America", The Tribe of Dina: A Jewish Women's Anthology, p. 37.
- Klepfisz, Irena. "Secular Jewish Identity: Yidishkayt in America", The Tribe of Dina: A Jewish Women's Anthology, p. 38.
- Klepfisz, Irena. "Secular Jewish Identity: Yidishkayt in America", The Tribe of Dina: A Jewish Women's Anthology, p. 39.
- Barnard College. "Irene Klepfisz" [faculty profile]. 2014.
- Kaye/Kantrowitz, Klepfisz. ‘’The Tribe of Dina: A Jewish Women’s Anthology’’, 1986, ISBN 0-931103-02-9, p7
- Mankiller, Wilma Pearl. The Reader's Companion to U.S. Women's History, Houghton Mifflin, 1998, ISBN 0-618-00182-4, p339
- Women;'s Review of Books"