[5] PML was poorly understood until described in the findings of Grignani et al in their 1996 study of patients with acute promyelocytic leukemia (APL).

The promoter region of the gene contains targets of signal transducers and activators of transcription (STATs), interferon regulatory factors, and p53 protein, indicating the intricacy of its involvement in cellular functions.

[11] In addition to regulation through alternative splicing, the protein product is subject to post-translational modifications such as acetylation and phosphorylation.

[9] PML phosphorylation triggers further modification through the attachment of SUMO proteins to the RING domain by UBC9 SUMO-conjugating enzyme,[5] which occurs in a cell cycle dependent way.

[11] PML is translated in the cytoplasm of the cell, but its N-terminus contains a nuclear localization signal which causes its import to the nucleus.

The exact significance of this association is unclear, however evidence suggests that PML-NBs may influence transcription at these specific gene sites.

In addition to this regulation of transcription, observations of PML-NBs have strongly suggested that the protein complex plays a role in mediating DNA-damage responses.

[5] In addition to those two apoptotic pathways, Fas-induced apoptosis relies on the PML-NBs to release FLICE-Associated huge protein, which then localizes to the mitochondria to promote the activation of Caspase-8.

[5] It has been shown to be involved with the formation of certain chromatin features of cells experiencing senescence, such as senescence-associated heterochromatin foci (SAHFs), which are believed to suppress the expression of growth-promoting factors and genes.

[14] Both humans and mice have been found to demonstrate an increased propensity for tumor formation upon loss of PML function.

PML disruption occurs in a wide variety of cancer types, and results in more metastatic tumors, and correspondingly poorer prognoses.

Many proteins involved in genomic stability maintenance rely on the PML-NBs for targeting, and PML loss thus leads to a decrease in repair efficiency within the cell.

[5] In addition to changes in numbers, PML-NBs also associate with different proteins over the lifetime of the cycle, and undergo significant biochemical changes in composition.

[5] It is thought that this may serve to preserve the orientation of the chromatids with which the PML-NBs are associated, or monitor the integrity of replication forks.