TSR2 is a ribosomal protein chaperone involved in 40S ribosomal subunit maturation and rRNA processing. 1 TSR2 functions as a chaperone for the ribosomal protein RPS26, a component of the 40S subunit, and plays an important role in noncanonical translation mechanisms. 1 In normal physiology, TSR2 contributes to ribosome biogenesis through participation in SSU-rRNA maturation from the tricistronic rRNA transcript. Pathogenic mutations in TSR2 are associated with Diamond-Blackfan anemia (DBA), a rare congenital bone marrow failure disorder characterized by erythroid hypoplasia. 2 3 TSR2 mutations represent a non-ribosomal protein gene cause of DBA, contributing to disrupted erythropoiesis and impaired red blood cell production through mechanisms including translational dysfunction and autophagy dysregulation. 2 Beyond ribosomopathies, TSR2 demonstrates tumor-suppressive functions. TSR2 overexpression induces apoptosis in laryngeal squamous cell carcinoma cells through NF-κB pathway inhibition 4 and suppresses gastric cancer cell proliferation and invasion via PI3K/AKT pathway downregulation. 5 Conversely, elevated TSR2 expression correlates with hypertension development through PPAR signaling pathway activation. 6 Thus, TSR2 functions as both a ribosome maturation factor essential for hematopoiesis and a multifunctional protein with disease-specific regulatory roles in cancer and cardiovascular pathology.