Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12202038, PubMed:12535518, PubMed:16168377, PubMed:16399501, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12202038, PubMed:16399501, PubMed:32322062). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:15899885, PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligases AMFR/gp78 and/or RNF139 (PubMed:12535518, PubMed:16168377, PubMed:22143767). Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78 (PubMed:28604676). Interacts with SCAP; interaction is direct and only takes place in the presence of sterols; it prevents interaction between SCAP and the coat protein complex II (COPII) (PubMed:15899885, PubMed:32322062). Associates with the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2); association is mediated via its interaction with SCAP and only takes place in the presence of sterols (PubMed:12202038, PubMed:16399501, PubMed:32322062). Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway (PubMed:12535518). Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway (PubMed:16168377, PubMed:22143767). Interacts with SOAT2/ACAT2; leading to promote recruitment of AMFR/gp78 and subsequent ubiquitination of SOAT2/ACAT2 (PubMed:28604676). Interacts with RNF139 (PubMed:20068067, PubMed:22143767). Interacts with RNF145 (PubMed:29374057). Expressed in all tissues tested with highest expression in the liver. By insulin (PubMed:9268630). Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation (PubMed:16399501). The KxHxx motif mediates association with the coatomer complex. Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4. Phosphorylation at Ser-207 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG1 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes. Ubiquitinated by AMFR/gp78 in response to sterol deprivation, leading to its degradation: when the SCAP-SREBP complex becomes dissociated from INSIG1, INSIG1 is then ubiquitinated and degraded in proteasomes (PubMed:16399501, PubMed:17043353). Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex (PubMed:16399501). Ubiquitinated by RNF139 (PubMed:20068067). Belongs to the INSIG family. Insig1 entry