Abstract: Myelodysplastic syndrome (MDS) is a heterogeneous myeloid tumor that originates from hematopoietic stem cells (HSCs) and is associated with a high risk of progression to acute myeloid leukemia (AML). Studies have shown that 90% of patients with MDS have gene mutations, of whom approximately 25% have SF3B1 mutations. In patients with MDS carrying this mutation, the TGF-β pathway is upregulated, inducing cell cycle arrest and thereby leading to erythroid ineffective hematopoiesis and pathological hematopoiesis. Luspatercept can be used as a ligand trap to capture TGF-β ligands, inhibit SMAD2/3 pathway activation, downregulate TGF-β pathway, and promote advanced red blood cell maturation. Currently, it has been approved by the Food and Drug Administration (FDA) for the treatment of anemia in patients with low-risk MDS, and studies have shown that the response rate is higher in patients with SF3B1 mutations. This article will review the current status of luspatercept in the treatment of SF3B1 mutation-related MDS; it will also analyze its effectiveness and safety and provide therapeutic strategies for clinical use.