PELP1 (Proline-, Glutamic acid-, and Leucine-rich protein 1) is a multi-domain scaffolding protein that serves diverse cellular functions. Primarily, PELP1 acts as a coregulator of nuclear receptors, particularly estrogen receptors, facilitating both genomic and non-genomic signaling pathways 1. The protein functions as a key component of the Rix1 complex involved in ribosome biogenesis, where it scaffolds WDR18, TEX10, and SENP3 2. Mechanistically, PELP1 contains multiple functional domains including eleven LxxLL motifs and serves as a substrate for various kinases, with phosphorylation regulating its activity in different complexes 3. In the nucleus, PELP1 participates in chr17 remodeling and transcriptional regulation, while in the cytoplasm it mediates rapid signaling through interactions with growth factor receptors and kinases like SRC 4. PELP1 expression is significantly upregulated in multiple cancers including breast, prostate, hepatocellular carcinoma, and others, where it promotes tumorigenesis, metastasis, and therapy resistance 5 6. Clinically, elevated PELP1 expression correlates with poor survival outcomes and serves as a prognostic biomarker 7. The protein represents a promising therapeutic target, with small-molecule inhibitors like SMIP34 showing efficacy in reducing cancer cell viability and tumor growth 6.