CBX5, also known as HP1α, is an epigenetic regulatory protein. It is a methyl reader that interprets H3K9me3 marks mediated by H3K9 methyltransferases, contributing to the formation of inaccessible heterochromatin and suppression of gene expression. CBX5 is involved in multiple biological processes, including maintaining chromatin state, and is associated with pathways relevant to cell growth, apoptosis, and fibroblast activation [1,4,5].

In myeloid leukemia, loss of RBMX/L1, which control the transcription of CBX5, led to changes in chromatin accessibility and leukemia development was delayed. Forced CBX5 expression rescued the effects of RBMX/L1 depletion on cell growth and apoptosis, indicating CBX5 is crucial for leukemia cell survival [1].

In lung cancer, CBX5 loss drives EGFR inhibitor resistance. CBX5-knockdown in EGFR-mutant lung adenocarcinoma cells increased E2F1 expression, which upregulated the anti-apoptotic gene BIRC5, attenuating apoptosis induction by EGFR inhibitors [2].

In periodontitis, Porphyromonas gingivalis OMVs' sRNA45033 targets CBX5, which regulates apoptosis through p53 DNA methylation [3].

In lung fibrosis, the CBX5/G9a/H3K9me-mediated gene repression is essential for fibroblast activation. Inhibition of this pathway elevates PGC1α, attenuating fibrosis [4].

In summary, CBX5 is vital for maintaining chromatin state, cell growth, apoptosis regulation, and fibroblast activation. Research using gene-knockout or related models in myeloid leukemia, lung cancer, periodontitis, and lung fibrosis has revealed its significant roles in these disease conditions, highlighting its potential as a therapeutic target in these areas.