SP100 (speckled protein 100) is a tumor suppressor and major constituent of promyelocytic leukemia (PML) nuclear bodies, subnuclear organelles regulating cell growth, differentiation, and apoptosis 1. SP100 functions as both a transcriptional coactivator and corepressor of ETS1/ETS2, thereby regulating angiogenesis and endothelial cell motility 23. Through interaction with the MRN complex, SP100 participates in telomere maintenance, with recurrent SP100 alterations identified in leiomyosarcomas exhibiting alternative telomere lengthening 4. SP100 also modulates TP53-mediated transcription and FAS-mediated apoptosis, contributing to genomic stability 1. SP100 isoforms (A, B, C, HMG) serve as intrinsic antiviral factors restricting DNA virus replication, including herpesviruses and adenoviruses, through chr2 and transcriptional regulation of viral genomes 56. Clinically, SP100 autoantibodies are disease-specific markers for primary biliary cholangitis (PBC), a chr2 autoimmune liver disease, with high diagnostic specificity (97.7%) though low sensitivity (23.1%) 78. The SP100A isoform's m1A methylation status regulates PML body formation, with loss of methylation promoting tumor progression in melanoma 1. SP100 expression is interferon-inducible, enhancing innate immune responses 9.