Abstract:Glycerol dialkyl glycerol tetraethers (GDGTs) are the main components of membrane-spanning lipids in the cell membranes of archaea and some bacteria. As molecular fossils, GDGTs are sensitive to changes in environmental variables, and GDGT-based proxies have unique advantages in quantitative reconstructions of marine and terrestrial paleoenvironment studies. Although GDGT-based proxies have been widely applied in extensive studies, researchers have increasingly concerned about their fidelity and applicability. The key point lies in the lack of research on the biosynthetic and physiological mechanisms of GDGTs, which results in the deficiency of molecular biological and physiological basis for GDGT-based proxies. Recent breakthroughs achieved with interdisciplinary collaboration in the biosynthesis of archaeal isoprenoid GDGTs provide a reliable biological basis and a new vision for the implication of lipid biomarkers. In this paper, we present a holistic review on the biosynthetic pathway of archaeal isoprenoid GDGTs, propose a hypothetic biosynthetic pathway of bacterial branched GDGTs, and discuss the biogeochemical implications of the physiological process of GDGTs. Finally, we provide an outlook for future research on GDGTs.