Ppm1g, also termed PP2Cγ, is a member of the PPM family. Its enzymatic activity depends highly on Mg2+ or Mn2+, and it acts as a dephosphorylation regulator for numerous key proteins. Ppm1g is involved in significant biological processes like eukaryotic gene expression regulation, DNA damage response, cell cycle, apoptosis, cell migration, cell survival, and embryonic nervous system development. It also regulates various signaling pathways [1].

In pancreatic cancer, Ppm1g depletion decreased cell growth in vitro and in vivo, and high Ppm1g expression was linked to short overall survival. Ppm1g was found to be a positive regulator of autophagy, promoting autophagy and proliferation of pancreatic cancer cells by upregulating HMGB1 [2].

In hepatic ischemia/reperfusion injury, inhibition of Ppm1g in a mouse model further promoted liver damage, hepatocyte apoptosis, and transaminases release, indicating that Ppm1g suppresses hepatic injury and macrophage M1 phenotype by repressing STING-mediated inflammatory pathways [3].

In cholangiocarcinoma, Ppm1g can be a therapeutic target as it inhibits epithelial-mesenchymal transition by catalyzing TET1 dephosphorylation [4].

In hepatocellular carcinoma, Ppm1G knockdown led to reduced tumor volume in vivo, and it was shown to promote cell proliferation by modulating mutant GOF p53 protein expression, as well as promote cell migration through mediating TBL1X mRNA splicing [5,6].

In lung adenocarcinoma, Ppm1G was highly expressed and its knockdown could affect proliferation, invasion, and metastasis. Ppm1G reduced p38 phosphorylation via MEK6 dephosphorylation [7].

In conclusion, Ppm1g plays diverse and crucial roles in multiple biological processes and is significantly involved in the progression of various cancers including pancreatic, cholangiocarcinoma, hepatocellular carcinoma, and lung adenocarcinoma. Gene knockout or knockdown models in these contexts have been instrumental in revealing its functions, highlighting its potential as a biomarker and therapeutic target for these diseases.