TASP1 (taspase 1) is a highly conserved threonine protease located on chromosome 20 that functions as a critical activator of histone methyltransferases and transcriptional regulators. Its primary function involves proteolytic cleavage and activation of KMT2A/MLL1 and KMT2D/MLL2 1, histone methyltransferases essential for transcription regulation. Beyond its canonical substrates, TASP1 cleaves TFIIA, a basal transcription factor critical for embryonic hematopoiesis and skeletal development 2, and processes Myo1f to regulate filopodia dynamics in immune cells 3. Through substrate activation, TASP1 controls expression of HOX genes and cell cycle regulators including CCNA1, CCNB1, CCNE1, and CDKN2A 1. In cancer contexts, TASP1 is upregulated and promotes proliferation and metastasis in gastric and gallbladder cancers via AKT/PI3K signaling pathways 45. Homozygous loss-of-function TASP1 variants cause Suleiman-El-Hattab syndrome, a neurodevelopmental disorder characterized by developmental delay, hypotonia, distinctive facial features, cardiovascular malformations, and skeletal abnormalities 67. This syndrome represents a histone modification disorder with methylation patterns intermediate between normal controls and Kabuki syndrome, underscoring TASP1's critical role in epigenetic gene regulation 68.