ANK1 (ankyrin 1) is a cytoskeletal protein primarily functioning in red blood cell membrane organization and structural integrity. The protein serves as a critical component of the red cell membrane skeleton, anchoring spectrin and other cytoskeletal elements to the plasma membrane 1. ANK1 also contributes to cellular organization beyond erythrocytes, potentially linking the sarcoplasmic reticulum to myofibrils in skeletal muscle and facilitating interactions between the Golgi and nuclear envelope 2. Pathogenic ANK1 variants cause hereditary spherocytosis (HS), a hemolytic anemia characterized by abnormal red cell morphology. ANK1 mutations account for approximately 49% of HS cases in pediatric populations 1. These mutations—predominantly frameshifts, nonsense, and splice-site variants—result in reduced ankyrin protein expression and loss of function 34. Patients with ANK1-HS typically present with moderate-to-severe transfusion-dependent hemolysis, often requiring splenectomy 3. Beyond hematologic disease, genome-wide association studies have identified ANK1 variants associated with type 2 diabetes risk in East Asian and European populations 56. Functional studies demonstrate that ANK1 is essential for pancreatic progenitor and skeletal muscle differentiation 7. Additionally, ANK1 overexpression suppresses osteosarcoma progression through ferroptosis promotion 8, suggesting broader roles in cancer biology.