TSEN15 is a non-catalytic subunit of the tRNA splicing endonuclease (TSEN) complex, which mediates intron removal from precursor-tRNA molecules 1. The TSEN complex, comprising TSEN2, TSEN15, TSEN34, and TSEN54, recognizes the mature domain of pre-tRNA and positions splice sites at the 5' and 3' ends into catalytic centers, cleaving introns while producing tRNA half-molecules with 2',3' cyclic phosphate and 5'-OH termini 1. The complex accommodates varying intron sequences through a molecular ruler mechanism independent of intron-specific sequences 1. Beyond tRNA processing, TSEN associates with pre-mRNA 3'-end processing factors, linking pre-tRNA splicing to mRNA maturation. Mutations in TSEN15 cause pontocerebellar hypoplasia 2F (PCH2F), characterized by progressive microcephaly, developmental delay, and intellectual disability 2. Disease-associated mutations destabilize TSEN15 protein and disrupt complex assembly, reducing pre-tRNA cleavage activity and generating imbalanced pre-tRNA pools in patient-derived cells 3. TSEN15 variants have also been associated with familial short stature 4. These findings establish TSEN15 as essential for proper brain development through its critical role in tRNA biogenesis.