Oxidosqualene-lanosterol cyclase (OSC) is a key enzyme in the biosynthesis of cholesterol. The catalytic Mechanism and the product specificity of OSC have herein been studied : using, QM/MM calculations:, According to our. Calculations, the protonation of the epoxide ring or oxidosqualene is rate limiting Wild type OSC (which generates lanosterol), and the mutants H232S (which generates parkeol) and H232T (which generates protosta-12,24-dien-beta-ol) were modeled, in order to explain the product specificity thereof. We show that the product specificity of OSC at the hydride/methyl-shifting stage is unlikely to be achieved by the stabilization of the cationic intermediates, as the precursor of lanosterol is in fact not the most stable cationic intermediate for wild type OSC. The energy barriers for the product determining conversions are instead found to be related to the product specificity of different OSC mutants, and we thus suggest that the product specificity of OSC is likely to be Controlled by kinetics,, rather than thermodynamics.