Pelp1, also known as Proline-, Glutamic acid-, and Leucine-rich protein 1, is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors [2]. It participates in multiple pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response [2]. Pelp1 is crucial as it interacts with various proteins involved in chromatin remodelling, DNA repair, and kinase signalling, playing an essential role in cellular functions [1]. Gene knockout (KO) and conditional knockout (CKO) mouse models have been valuable in studying Pelp1's functions.

PELP1 forebrain-specific knockout mice demonstrated its critical role in mediating both extranuclear and nuclear ER signalling in the brain, as well as E2-induced neuroprotection, anti-inflammatory effects, and regulation of cognitive function [1]. In cancer research, suppression of PELP1 expression using short hairpin RNA significantly reduced the cell viability, clonogenicity, and invasion of hepatocellular carcinoma (HCC) cells [3]. In glioblastoma, knockdown of PELP1 led to a significant decrease in cell viability, survival, migration, and invasion, and also increased the survival of mice implanted with U87 and GBM PDX models [4].

In conclusion, Pelp1 is a key regulator in multiple biological processes. Its functions in the brain, as revealed by KO mouse models, are essential for maintaining normal neural functions related to oestrogen signalling. In cancer, loss-of-function experiments show that Pelp1 plays a significant role in tumour cell survival and invasion, making it a potential therapeutic target for cancers such as HCC and glioblastoma.