TPR (translocated promoter region) is a major structural protein of the nuclear pore complex (NPC) that forms the basket-like structure on the nucleoplasmic side 1. Beyond its scaffolding role in nucleocytoplasmic transport, TPR functions in multiple critical cellular processes. It regulates nuclear export of unspliced mRNAs and negatively modulates translation initiation of CTE-containing transcripts [UniProt]. TPR also protects cells from RNA-mediated replication stress by coordinating transcription, splicing, and mRNA export machinery through interactions with TREX-2 complex components like GANP 2. During mitosis, TPR acts as a spatial regulator of the spindle-assembly checkpoint, recruiting checkpoint proteins to unattached kinetochores [UniProt]. TPR is essential for heterochromatin organization at the nuclear periphery and mediates the formation of cytoplasmic chr1 fragments during senescence, which activates innate immune signaling and the senescence-associated secretory phenotype 3. The protein's N-terminal TPR domain enables interactions with other proteins like G3BP1 in stress granule regulation 4. Dysregulation of TPR is implicated in cancer development, and mutations cause autosomal recessive intellectual developmental disorder 79 1, highlighting its importance in genomic stability and neurological function.