TSR3 (TSR3 ribosome maturation factor) is an aminocarboxypropyltransferase that catalyzes the final step in synthesis of the hypermodified pseudouridine m1acp3-Psi at position 1248 in eukaryotic 18S rRNA 1. This modification is essential for proper ribosomal small subunit (40S) maturation and function. TSR3 plays critical roles in cellular fate determination and disease pathogenesis. During neural crest development, TSR3-mediated 18S rRNA modification (m¹acp³ψ at U1248) is specifically associated with mesenchymal fate commitment; disrupting TSR3 perturbs cranial neural crest differentiation in vitro and in vivo, leading to craniofacial malformations 1. In cancer, TSR3 depletion preferentially inhibits proliferation of NPM1-mutant acute myeloid leukemia (AML) cells by activating p53-dependent apoptosis, and can restore sensitivity to venetoclax in therapy-resistant NPM1c+ AML 2. Similarly, in glioblastoma, high TSR3 expression confers resistance to the anti-tumoral GJB1-13k protein, suggesting TSR3 as a therapeutic target 3. Additionally, DNA methylation at the TSR3 locus was identified in a meta-analysis as associated with atopic asthma in children and adolescents 4. These findings establish TSR3 as a critical regulator of ribosome maturation with implications for developmental patterning, cancer therapy resistance, and immune-related diseases.