SS18L2 is an epigenetic modifier protein that functions as a transcriptional co-activator through protein-protein interactions 1. The protein contains an SNH domain that serves as a major interface for interactions with various proteins involved in gene regulation 1. SS18L2 can functionally substitute for its paralog SS18 in protein-protein interactions, indicating functional conservation within the SS18 protein family 1. The gene is composed of three exons and maps to chromosome 3, representing a smaller structure compared to related SS18 family members 2. In cancer biology, SS18L2 functions as an essential regulator of cell fitness; CRISPR/Cas9 screening identified SS18L2 as a growth-regulatory epigenetic modifier in triple-negative breast cancer (TNBC) cells, demonstrating its importance for cancer cell survival under both in vitro and in vivo conditions 3. These findings suggest SS18L2 represents a potential therapeutic target in epigenetically-driven cancers, particularly TNBC. The SS18L2 locus likely originated from an earlier genomic duplication event in the vertebrate lineage, distinguishing it from the more recent duplication giving rise to SS18 and SS18L1 1.