<p>External stress conditions can induce disturbances in the internal environment of cells, sufficient for protein misfolding or membrane disorganization. To cope with this phenomenon, cells have developed several strategies, including the production of heat stress proteins (HSPs). These include small heat shock proteins (sHSPs). sHSPs share a characteristic three-dimensional architecture, with a central α-crystalline domain (ACD) flanked by two terminal domains. This structural organization enables them to form a variety of oligomeric complexes, giving these proteins their function. As large oligomers, all sHSPs act as chaperones. Conversely, some of them adopt a lipochaperone role when present in dimeric form. While the role of the ACD domain in oligomerization and the mechanism of action of sHSPs has been studied extensively, the functions of the terminal domains, in particular the N-terminal domain, remain poorly explored. In this context, the role of the N-terminal domain of sHSP Lo18, produced by the bacteria <i>Oenococcus oeni</i>, was investigated. To assess its importance, a truncated protein, depleted of the first 27 amino acids, was compared with the wild-type protein. Analyses focused on the oligomeric structure, the ability to prevent protein aggregation, and the ability to maintain membrane fluidity. In parallel, the involvement of the N-terminal domain in the interaction between Lo18 and membranes was examined by RP-HPLC. The results reveal that Lo18’s N-terminal domain plays a decisive role, both in the formation and stabilization of oligomeric structures, and in interaction with protein and lipid substrates, essential parameters in chaperone and lipochaperone activity.</p>