Councillors are due to consider a proposal to build an eight-storey building containing four townhouses and 45 flats in Otago Lane, which backs on to the River Kelvin at Hillhead.
The latest development bid has infuriated local people who have lodged almost 800 letters of objection, as well as a petition signed by more than 3500 people.
Those against the scheme include MSPs Patrick Harvie and Sandra White; MPs Alan Reid, Jo Swinson and Alistair Carmichael; local councillor Martha Wardrop; Hillhead Community Council; and Woodlands And Park Community Council.
The controversy over the site began in 2009, when Otago Street Developments lodged an application to build 142 homes on the site, but it was later withdrawn after protests.
The company is now hoping to get the go-ahead for a new development and has won the backing of planners.
It wants to build 10 one-bedroom flats, 20-two bedroom, 15 three-bedroom and four townhouses, each with four bedrooms.
But local people are outraged at the move and point out that the Save Otago Lane campaign, which was launched three years ago, has attracted more than 4000 letters of objection for the two different sets of plans.
Last October, more than 300 people marched through the West End in protest at the latest plan.
Campaigner Martin Fell, of the Tchai-Ovna tea house, which is based in the lane, said business owners fear disruption caused by the building of such a large project will force them to close.
Iain Steel, chairman of Otago Lane Community Association, said: "If Glasgow City Council approves these plans it is possible these four-bedroom dwellings, once built, can be subdivided, bringing the number of dwellings up to over 49.
"We could be looking at about 200 people moving into a lane that has only one narrow access."
Hillhead Green councillor Martha Wardop described the building as "a monstrous eight storey flatted development that would destroy the historic lane and wildlife habitats along the River Kelvin".
However, city planners have recommended the scheme gets the go-ahead.
A report to councillors states: "It is considered the scheme now proposed represents a contemporary design that will enliven this part of the conservation area.
"Historic maps until the mid-1980s show a solid frontage of development on to the river edge along the full width of the application site.
"This evidence shows there is an historic precedent for development in close proximity to the river edge."
The company was not available for comment.