Significance The multifaceted involvement of GM1 as a ligand in many cellular functions has been well recognized. We find that GM1 readily desorbs from the membrane of cell-sized model biomimetic systems (giant unilamellar vesicles). The desorption is unbalanced, creating an asymmetry between the bilayer leaflets. This results in reshaping weakly curved membranes into nanotubular invaginations stabilized by the membrane spontaneous curvature, which we quantify experimentally. Computer simulations confirm the experimental results. Uncovering the role of GM1 as a fine regulator of membrane curvature broadens our perspective on its important function in reshaping neuronal membranes and emphasizes that GM1 desorption can strongly affect the cell membrane morphology.