RPS6KA5 encodes a serine/threonine protein kinase belonging to the p90RSK (ribosomal S6 kinase) family that plays crucial roles in cellular signaling and gene regulation 1. The protein functions as an epigenetic modifier that regulates gene expression through histone phosphorylation, particularly phosphorylating histone H3 at serine 28 (H3S28), which leads to transcriptional activation of target genes 2 3. RPS6KA5 is involved in multiple cellular processes including cell proliferation, inflammation, and stress responses by phosphorylating transcription factors such as CREB and components of the NF-κB pathway 3. In cancer contexts, the gene shows complex roles - it can promote colorectal cancer metastasis through epithelial-mesenchymal transition pathways 4, while also being identified as a potential biomarker in thyroid cancer 5. The gene demonstrates tissue-wide expression patterns across 16 human tissues and is localized to chromosome 14-32.1 1. Clinically, RPS6KA5 methylation status has emerged as a potential predictor of treatment response in adolescent major depressive disorder, suggesting its relevance in psychiatric conditions 6. These findings highlight RPS6KA5 as a multifunctional kinase with significant roles in normal physiology and disease pathogenesis.