[8][9] PELP1 plays essential roles in hormonal signaling, cell cycle progression, and ribosomal biogenesis.

[35] Studies using TG mice model suggested the existence of an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis [39] 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.

[40] PELP1 is needed for optimal DNA damage response, is phosphorylated by DDR kinases and is important for p53 coactivation function.

Mechanistic studies showed that PELP1 interaction with the arginine methyltransferase PRMT6 plays a role in RNA splicing.

[10][14] PELP1 plays an essential role in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain.

[47][48][49] PELP1 deregulation in vivo promotes development of mammary gland hyperplasia and carcinoma [39] PELP1 is implicated in progression of breast,[31][38][47][50] endometrial,[18] ovarian,[37] salivary[51] prostate,[22][23] lung,[52] pancreas,[53] and colon[54] neoplasms.

[57] AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence.

[58] 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.

PELP1 expression is an independent prognostic predictor of shorter breast cancer–specific survival and disease free interval.

[38] Treatment of breast and ovarian cancer xenografts with liposomal PELP1–siRNA–DOPC formulations revealed that knockdown of PELP1 significantly reduce the tumor growth.

Since PELP1 lacks known enzymatic activity, drugs that target PELP1 interactions with other proteins should have clinical utility.