SPIN4 is an X-linked histone reader protein that recognizes acetylated and methylated histone marks, including H3K4me3 and H4K20me3 1. Through its chrX-binding activity, SPIN4 promotes canonical WNT signaling and negatively regulates cell proliferation 1. Protein stability of SPIN4 is controlled by the E3 ubiquitin ligase DCAF16, which ubiquitinates SPIN4 for degradation, with counterbalancing deubiquitination by BAP1 23. Loss-of-function variants in SPIN4 cause X-linked overgrowth syndrome, a condition characterized by generalized prenatal-onset overgrowth and increased longitudinal bone growth 14. Mechanistically, SPIN4 loss impairs WNT signaling in growth plate chondrocytes, leading to increased proliferation and altered progenitor populations 1. Additionally, SPIN4-deficient mice exhibit increased tumor prevalence at 18 months, indicating associations with malignancy risk 5. Beyond growth regulation, SPIN4 plays context-dependent roles in disease. In cervical cancer, HPV16 E7 enhances cancer stem cell properties through an APC2-SPIN4 axis promoting WNT/β-catenin signaling 6. SPIN4 expression levels correlate with pediatric Wilms tumor prognosis 7. In *C. elegans*, spin-4 regulates phosphatidylcholine synthesis and ferroptosis susceptibility 8, suggesting broader metabolic functions beyond epigenetic regulation.