NKAP (NFKB activating protein) is a multifunctional nuclear protein that primarily acts as a transcriptional repressor with critical roles in RNA metabolism and genome stability. As a transcriptional corepressor, NKAP associates with HDAC3 to regulate Notch-mediated signaling required for T-cell development, with NKAP deficiency blocking αβ T-cell development while causing upregulation of Notch target genes 1. NKAP localizes to nuclear speckles and functions as an RNA-binding protein involved in pre-mRNA splicing, interacting with various splicing factors including FUS/TLS 2. Mechanistically, NKAP works with HDAC3 to prevent R-loop accumulation and maintain genome integrity, with NKAP depletion causing DNA damage and replication fork defects 3. NKAP also protects cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m6A-dependent manner 4. Disease relevance includes associations with X-linked intellectual developmental disorder (Hackman-Di Donato type) 5, while paradoxically functioning as an oncogene in pancreatic and colon cancers through mTOR/Akt pathway activation 67. The diverse roles of NKAP in transcriptional regulation, RNA processing, and genome stability highlight its importance in normal development and disease pathogenesis.