PBXIP1 (PBX homeobox interacting protein 1) is a multifunctional coregulator with diverse roles spanning development, cell migration, and disease. Primarily, PBXIP1 acts as a transcriptional corepressor of PBX homeobox proteins, inhibiting PBX1-HOX complex DNA binding and blocking E2A-PBX1 transcriptional activity 1. Beyond transcriptional regulation, PBXIP1 functions as a noncanonical guanine nucleotide exchange factor for Rab5, localizing to focal adhesions and endosomal compartments where it regulates focal adhesion disassembly, integrin trafficking, and cell migration 2. Additionally, PBXIP1 tethers estrogen receptor-alpha to microtubules, influencing estrogen signaling. PBXIP1 is critical during development, with expression detected in definitive endoderm and pancreatic lineages during embryogenesis 3, and playing essential roles in chondrogenesis during limb development 4. Clinically, PBXIP1 emerges as a significant cancer biomarker. High PBXIP1 expression correlates with poor prognosis, metastatic spread, and epithelial-mesenchymal transition in colorectal cancer 5, and associates with worse outcomes across multiple cancer types 1. Recent multi-omics analysis identified PBXIP1 as critically associated with Alzheimer's disease neuropathological traits (β-amyloid, tau tangles) and clinical diagnosis, potentially through roles in astrocytes and hippocampal neurons via the mTOR pathway 6. PBXIP1 dysregulation also links to renal fibrosis, chr1 kidney disease, and osteoarthritis, highlighting its importance in pathological conditions.