SAP130 (spliceosome-associated protein 130) is a multifunctional protein with roles in transcriptional repression and immunological signaling. As a component of the SF3b RNA splicing complex and transcription complexes like STAGA/TFTC 1, SAP130 functions in pre-mRNA splicing regulation, with mutations causing differential splicing defects and cell-cycle arrest in yeast 2. Beyond its classical splicing roles, SAP130 serves as a critical mediator of hepatocyte-macrophage crosstalk in inflammatory disease. Upon ferroptosis induction, SAP130 is released from damaged hepatocytes and acts as a damage-associated molecular pattern (DAMP), binding to macrophage-inducible C-type lectin (Mincle) 34. This SAP130-Mincle interaction activates Syk signaling and promotes M1 macrophage polarization, exacerbating inflammation 35. In disease contexts, serum SAP130 levels correlate significantly with Crohn's disease severity and predict response to enteral nutrition therapy 6. Additionally, SAP130 associates with cullin-RING ubiquitin ligase complexes in a Nedd8-dependent manner, potentially linking protein ubiquitination to gene expression regulation 1. These findings establish SAP130 as both a splicing regulator and an immunological danger signal with therapeutic implications for inflammatory and infectious diseases.