INTS12 (integrator complex subunit 12) is a component of the integrator complex that functions as a genome-wide transcriptional attenuator by regulating RNA polymerase II (RNAPII) elongation. The protein acts through multiple mechanisms including RNA cleavage and phosphatase modules to control transcriptional elongation 1. INTS12 binds throughout the genome at transcriptionally active regions and regulates protein synthesis pathways, with knockdown leading to decreased protein translation and dysregulation of genes relevant to airway biology 2. Beyond its canonical role in snRNA processing, INTS12 demonstrates context-dependent functions in maintaining genome integrity by linking ribotoxic stress responses to transcription-coupled nucleotide excision repair through interaction with CSB and facilitating RNAPII clearance 3. The gene shows clinical significance in respiratory health, as genetic variants at the INTS12-GSTCD locus on chromosome 4 are associated with lung function measures including FEV1, with INTS12 expression correlating with lung function parameters 42. Additionally, INTS12 has been implicated in cancer therapy resistance, where it mediates resistance to CAR T-cell therapy in pancreatic cancer through transcriptional regulatory mechanisms 5. The protein is predominantly expressed in epithelial cells and pneumocytes in lung tissue 6.