SPIN1 (Spindlin 1) is a chr9 reader that recognizes histone H3 methylation marks and coordinates multiple cellular processes. Mechanistically, SPIN1 specifically binds histone H3 trimethylated at lysine 4 and lysine 9 (H3K4me3K9me3) 1, as well as H3K4me3 with asymmetrically dimethylated arginine 8 (H3R8me2a) 2. In male germ cells, SPIN1 serves as a critical authentication factor in piRNA-directed DNA methylation: it recognizes young LINE1 transposons marked with H3K4me3K9me3 and recruits PIWIL4 and SPOCD1 to promote transposon silencing 1. SPIN1 also activates Wnt signaling and promotes rRNA gene expression 2. In cancer, SPIN1 overexpression promotes tumorigenesis and therapy resistance through multiple mechanisms. SPIN1 acts as a proto-oncogene in seminoma by reducing apoptosis and upregulating CYCD1 3, while in non-small cell lung cancer, it confers radioresistance via the FOXO3a/FOXM1 axis 4. SPIN1 facilitates homologous recombination-mediated DNA repair by promoting H3K9me3-dependent Tip60 recruitment 5, contributing to chemoresistance 5. SPIN1 is elevated in gastric cancer and correlates with poor prognosis and epithelial-mesenchymal transition 6. Clinically, SPIN1 represents a promising therapeutic target in multiple cancer types 2.