The building opened as a synagogue in 1874
The city's Jewish community has a long history going back almost 300 years to when Sephardi Jews from the Iberian Peninsula first settled in Manchester.
It was to serve this growing community that a synagogue was built on Cheetham Hill Road, which is now home to the Jewish Museum.
But this is a museum like no other in Manchester as the building itself, complete with its Moorish architecture, is faced with becoming the latest chapter in the city's Jewish history.
It's now appealing to the Jewish community for donations which it says are vital for its survival.
The museum is a registered charity and chair of the trustees, Anne Millan, said the Grade II listed building is almost exactly as it was when it opened in 1874.
"It's very special," she said. "It's the only Jewish museum outside London. The downstairs, where the men would sit in the synagogue, is completely unchanged today."
Indeed, the museum has an authentically religious feel: facing Jerusalem is the menorah window; beneath the window, the Ark, holding the Torah Scrolls, and the bimah, where the rabbi conducted the service.
It's only the upstairs gallery that's been adapted for exhibitions on Jewish Religion and Practices, Jewish History, Family Life, the Holocaust, Prejudice & Discrimination.
Stuart Hilton, the museum's financial director said the Jewish Museum had an important role to play, particularly for the many school parties that visit each year.
"It's the only one of its kind in the country that has a unique set of collections representing the whole of a unique community that settled here in Manchester from the 1740s."
"They come here primarily to learn about the Jewish way of life, but underneath that there is a message that we've always put out about fighting racism, about social cohesion, and it's so important."
It's not the first time the building has faced closure.
The menorah window faces Jerusalem
At the turn of the century, the area of Cheetham Hill was a thriving Jewish area with a number of synagogues up and down Cheetham Hill Road.
Among them were the mighty Great Synagogue and the Reform Synagogues, but these soon fell victim to the prosperity of the Jewish community, as Anne Millan explained.
"As Jews became wealthier, they wanted to move out of the slum areas of Manchester and they went either north to the areas of Prestwich and Whitefield, or south to Cheadle and Didsbury."
"To observe the Jewish faith in an orthodox fashion, you must not drive or be driven on the Sabbath. So most Jews need their synagogue to be within walking distance."
While others fell derelict, the Spanish and Portuguese Synagogue found a new purpose and, in 1984, re-opened as the Jewish Museum.
Twenty-five years later, its challenge now is to avoid becoming part of the city's compelling Jewish history it's trying to chronicle.