HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, representing the rate-limiting step in cholesterol and isoprenoid biosynthesis 1. As the primary target of statins, HMGCR plays a critical role in cellular cholesterol homeostasis 2. Beyond its metabolic function, HMGCR has emerged as a key autoantigen in immune-mediated necrotizing myopathy (IMNM), where anti-HMGCR autoantibodies cause myofiber necrosis and severe proximal weakness 3. Anti-HMGCR myopathy is strongly associated with statin exposure but also occurs in statin-naïve patients and juveniles, suggesting diverse pathogenic mechanisms 4. Notably, anti-HMGCR antibodies appear directly pathogenic, as demonstrated in animal models 5. Recent studies reveal HMGCR's broader cellular roles: BRCC36-mediated deubiquitination of HMGCR regulates the balance between ferroptosis and pyroptosis in hepatocellular carcinoma 6, while tumor-derived exosomal miR-9-5p enhances HMGCR expression to promote breast cancer liver metastasis 7. Additionally, SOX18 transcriptionally regulates HMGCR within an endothelial mevalonate pathway axis controlling infantile hemangioma pathogenesis, offering statin repurposing potential 8. These findings establish HMGCR as both a central metabolic enzyme and a disease-relevant autoimmune target with emerging roles in cancer and vascular biology.