Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. O2 + reduced [NADPH--hemoprotein reductase] + squalene = (S)-2,3-epoxysqualene + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] Inhibited by NB-598 ((E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bi-thiophen-5-yl)methoxy]benzene-methanamine). Contrary to fungal enzymes, the mammalian enzyme is only slightly inhibited by terbinafine. Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 2/3. Interacts (via N-terminal domain) with MARCHF6. Interacts with SMIM22; this interaction modulates lipid droplet formation. Detected in lever (at protein level). The C-terminal hydrophobic region contains two helices that mediate interaction with membranes. Contrary to predictions, this region does not contain transmembrane helices. The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high. The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices. The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions. Ubiquitinated by MARCHF6 in response to high cholesterol levels in intracellular membranes, leading to proteasomal degradation. Belongs to the squalene monooxygenase family.