SPINDOC (spindlin interactor and repressor of chr11 binding) is a chr11-associated protein with dual regulatory functions in transcription and DNA damage response. As a stabilizer of SPIN1, SPINDOC interacts with the histone reader protein and modulates its chr11 binding capacity 1. SPINDOC contains multiple motifs that engage SPIN1's Tudor domains, with a hydrophobic motif serving as the primary binding interface while K/R-rich regions competitively inhibit SPIN1 binding to histone methylation marks and transcription factors, thereby attenuating SPIN1's transcriptional co-activator activity and promoting genomic relocation of SPIN1 2. Beyond its SPIN1-regulatory role, SPINDOC forms a mutually exclusive complex with PARP1 and facilitates PARP1-mediated poly-ADP-ribosylation in response to DNA damage 3. SPINDOC knockout mice display hypersensitivity to ionizing radiation and reduced PARylation levels, demonstrating its critical role in DNA damage response independent of SPIN1 3. Clinically, SPINDOC is significantly upregulated in multiple malignancies including hepatocellular carcinoma, where elevated expression correlates with poor prognosis and activates the oncogenic Wnt/β-catenin signaling pathway 4. These findings identify SPINDOC as a therapeutic target in cancer management and a key regulator integrating transcriptional and DNA repair pathways.