The tRNA-splicing endonuclease complex is responsible for identifying and cleaving pre-tRNA at both 5’ and 3’ splice sites, thereby releasing introns and free tRNA molecules with 2',3' cyclic phosphates and 5'-OH termini. In addition to its role in pre-tRNA splicing, the heterotetrameric endonuclease complex participates in mRNA processing and, via its association with pre-mRNA processing factors, is thought to link pre-tRNA and pre-mRNA splicing events. TSEN2 (tRNA-splicing endonuclease subunit Sen2), also known as tRNA-intron endonuclease Sen2, is a 465 amino acid nuclear protein that constitutes one of the two catalytic subunits of the tRNA-splicing endonuclease complex. There are three isoforms of TSEN2 that are produced as a result of alternative splicing events. Isoform 1 seems to carry the active site for 5’-splice site cleavage. Defects in the gene encoding TSEN2 are the cause of pontocerebellar hypoplasia type 2B, which is characterized by progressive microencephaly with epilepsy, extrapyramidal dyskinesia and chorea without spinal cord findings.