Case 1: Six months ago, patient 1 presented with rhabdomyolysis with a CK of 17,622 Units/L. The statin was discontinued at that time, after which the patient noted substantial improvement in muscle symptoms. Two months later the patient was readmitted for complaints related to continued rhabdomyolysis. CK was elevated at 9800 Units/L, raising suspicion for SINAM. Physical exam findings on readmission were pertinent for 4/5 strength in proximal flexion and extension of the upper extremities bilaterally and 4/5 strength in hip flexion. Pertinent lab values on readmission include increased ALT of 122 Units/L, AST of 103 Units/L, TSH of 7.4 mIU/L, HbA1c of 6.6%, and BUN of 14.5 mg/dL. Urinalysis is positive 3+ for glucose, 1+ for ketones, and 2+ for blood. Brain MRI without contrast negative for any brain malignancies or abnormalities. Case 2: Patient 2 presented with gradual proximal muscle weakness while taking a statin for the past six months. Physical exam was notable for 4/5 strength in the biceps and triceps and 3/5 deltoid strength bilaterally. There was 4/5 strength in the knee flexors and extensors with 3/5 strength in the hip flexors bilaterally. Notable lab values include CK of 10,449 Units/L, CK-MB of 492ng/mL, fasting glucose of 160 mg/dL, ALT of 229 Units/L, and HgbA1C of 7.3%. Urinalysis was positive 3+ for glucose, 1+ for ketones, and 2+ for blood. Discussion: Statin induced necrotizing autoimmune myopathy (SINAM) is a rare complication of statin therapy in which subjects develop an immune response to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). SINAM’s pathophysiology remains poorly understood. Studies have shown that statins upregulate expression of HMGCR which serve as antibody targets in SINAM (Mohassel & Mammen, 2013). The HMGCR protein is upregulated in regenerating muscle fibers thus preferentially allowing autoantibodies to bind (Mammen et al, 2011). Additionally, complement is implicated in pathogenicity of SINAM with a study showing that C3 deficient mice had less pronounced deficiency in muscle strength (Bergua et al, 2019). This is further reinforced with a muscle biopsy in another SINAM confirmed patient showed C5b-9 sarcolemmal deposits (Sharma et al, 2019). This implicates the formation of antigen-antibody-complement complexes typical of a type III hypersensitivity reaction. Additionally, genetic risk factors for autoimmunity are important to consider. There is an association of SINAM occurrence in individuals with single nucleotide polymorphism in the SLCO1B1 that regulates hepatic uptake of drugs such as statins (SEARCH, 2008). HLA- DRB1*11:01 is associated with the formation of autoantibodies in SINAM (Mammen, 2016). Recent studies show the triple induction therapy of steroids, IVIG, and a steroid sparing immunosuppressant has been very effective (Meyer et al, 2020).