PELP1 functions as a coactivator of several NRs and regulates genes involved in proliferation and cancer progression. PELP1 enhances transcription functions of  ESR1, ESR2, AR, GR,  E2F and STAT3.   PELP1 participates in activation of ESR1 extra-nuclear actions by coupling ESR1 with Src kinase PI3K STAT3  ILK1  and mTOR PELP1 participates in E2-mediated cell proliferation and is a substrate of CDK4/cyclin D1, CDK2/cyclin E and CDK2/cyclin A complexes.  Studies using TG mice model suggested the existence of an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis 
PELP1 has a histone binding domain;  functions as a reader of histone modifications, interacts with epigenetic modifiers such as HDAC2, KDM1, PRMT6, CARM1; and  facilitates activation of genes involved in proliferation and cancer progression.  PELP1 modulates the expression of miRs, PELP1-mediated epigenetic changes play important role in the regulation miR expression and many of PELP1 mediated miRS are involved in promoting metastasis. PELP1 is needed for optimal DNA damage response, is phosphorylated by DDR kinases and is important for p53 coactivation function. PELP1 also interacts with MTp53, regulates its recruitment, and alters MTp53 target gene expression. PELP1 depletion contributes to increased stability of E2F1. PELP1 binds RNA, and participates in RNA splicing. The PELP1-regulated genome includes several uniquely spliced isoforms. Mechanistic studies showed that PELP1 interaction with the arginine methyltransferase PRMT6 plays a role in RNA splicing.
PELP1 plays critical roles in 60S ribosomal subunit synthesis and ribosomal RNA transcription. The SENP3-associated complex comprising PELP1, TEX10 and WDR18 is involved in maturation and nucleolar release of the large ribosomal subunit. SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling. Modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes.
PELP1 is widely expressed in many regions of  brain, including the hippocampus, hypothalamus, and cerebral cortex. PELP1 interacts with ESR1, Src, PI3K and GSK3β in the brain. It is essential for E2-mediated extra-nuclear signaling following global cerebral ischemic.   PELP1 plays  an essential role in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain. Ability of E2 to exert  anti-inflammatory effects was lost in PELP1 forebrain-specific knockout mice, indicating a key role for PELP1 in E2 anti-inflammatory signaling.
PELP1 is a proto-oncogene  that provides cancer cells with a distinct growth and survival advantage.  PELP1 interacts with various enzymes that modulate the cytoskeleton, cell
migration, and metastasis.  PELP1 deregulation in vivo promotes development of mammary gland hyperplasia and carcinoma  PELP1  is implicated in progression of  breast, endometrial, ovarian, salivary prostate, lung, pancreas, and colon neoplasms.
PELP1 signaling contributes to hormonal therapy resistance.  Altered localization of PLP1 contributes to tamoxifen resistance via excessive activation of the AKT pathway  and cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of tamoxifen. AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence. Cytoplasmic localization of PELP1 upregulates pro-tumorigenic IKKε and secrete inflammatory signals, which through paracrine macrophage activation, regulate the migratory phenotype associated with breast cancer initiation.