SET (SET nuclear proto-oncogene) is a multifunctional protein with critical roles in apoptosis, transcription, and chr9 regulation. As an anti-apoptotic factor, SET isoform 2 inhibits granzyme A-activated DNase NME1 during cytotoxic T-lymphocyte-induced apoptosis; cleavage of SET by GZMA disrupts this protective interaction. SET functions as a potent inhibitor of protein phosphatase 2A and histone acetyltransferase (HAT) activity, particularly targeting histone H4 acetylation, thereby silencing HAT-dependent transcription and preventing active DNA demethylation. SET promotes adenoviral DNA replication, with isoform 2 demonstrating higher specific activity. In cancer biology, SET overexpression correlates with unfavorable prognosis in lung tumors 1. SET interacts with transcription factor ZBTB11 to promote lung cancer cell migration and invasion through MMP9 transcriptional activation and PRRG2 repression, driving metastasis through YAP1 pathway activation 1. Additionally, SET-NUP214 fusion proteins interact with MLL to enhance HoxA10 gene promoter activity in T-cell acute lymphoblastic leukemia 2. These multifaceted functions position SET as a key regulator of cellular survival, gene expression, and cancer progression. Notably, mutations in SET cause intellectual developmental disorder, autosomal dominant 58, highlighting its importance in normal neurological development.