PPM1F, also known as CaMKP/POPX2, is a serine/threonine phosphatase belonging to the metal-dependent protein phosphatase (PPM) family. It binds manganese/magnesium ions in its active center and plays a crucial role in regulating multiple biological processes. PPM1F controls integrin activity by selectively dephosphorylating the T788/T789 motif in the integrin β cytoplasmic domain, which acts as a phospho-switch determining integrin activator or suppressor association [1]. It is also involved in intracellular signal transduction pathways, regulating kinases like Ca2+/calmodulin-dependent protein kinases (CaMKs) and AMP-activated protein kinase [5].

Disruption of the ppm1f gene in mice results in early embryonic death at day E10.5, indicating its essential role in embryonic development [1]. In the context of mental diseases, knockout of PPM1F in the dentate gyrus (DG) of the hippocampus produces antidepressant phenotypes under stress conditions, while its overexpression in DG leads to depression-related behaviors and increased neuronal excitability [2]. In anxiety-related studies, adeno-associated virus-mediated overexpression of PPM1F in the DG causes more pronounced anxiety-related behavior in female mice, suggesting its role in anxiety-related behaviors [3]. In methamphetamine (METH) addiction, knockout of PPM1F in the dorsal raphe nucleus (DRN) 5-HT neurons enhances susceptibility to METH-induced conditioned place preference, while overexpression attenuates it [4]. In ovarian cancer, knockdown of PPM1F inhibits tumor formation [6].

In summary, PPM1F is vital for embryonic development. Its knockout/conditional knockout mouse models have revealed its significance in mental diseases such as depression and anxiety, as well as in METH addiction and ovarian cancer. These studies help to understand the biological functions of PPM1F and its potential as a therapeutic target in related disease areas.