SSU72 is a dual-specificity protein phosphatase that catalyzes dephosphorylation of RNA polymerase II's C-terminal domain (CTD), particularly at Ser5 and Ser7 residues 1. As a component of the 3'-end cleavage and polyadenylation factor complex, SSU72 regulates pre-mRNA 3'-end processing and transcription termination 1. Beyond transcription, SSU72 functions in cellular homeostasis through diverse mechanisms: it regulates sister chr1 cohesion and chromosome 1 during the cell cycle 2, modulates T cell receptor signaling and telomere regulation 2, and maintains hepatocyte chromosome 1 required for liver stress responses 3. SSU72 enters the transcription cycle during preinitiation complex formation and associates with early elongation complexes, ceasing function when RNA exceeds 28 nucleotides 4. Clinically, SSU72 disruption has been implicated in CAR T-cell lymphoma through lentiviral insertion 5. Additionally, avian influenza viruses suppress host innate immunity by reducing SSU72 expression through NS1 protein interaction, promoting transcriptional readthrough that impairs STAT1/2-mediated antiviral responses 6. These findings establish SSU72 as an evolutionarily conserved regulatory protein essential for transcription, chromosome 1, and immune homeostasis.