Ppm1f, also known as CaMKP/PPM1F/POPX2, is a serine/threonine phosphatase belonging to the PPM (protein phosphatase, Mg2+/Mn2+-dependent) family [5]. It plays crucial roles in 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, potentially regulating Ca2+/calmodulin-dependent protein kinases and other protein kinases [5].

Disruption of the ppm1f gene in mice results in early embryonic death at day E10.5, highlighting its essentiality in 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 enhanced neuronal excitability [2]. In anxiety-related studies, adeno-associated virus-mediated overexpression of PPM1F in the DG leads to more pronounced anxiety-related behavior in female mice [3]. Regarding drug addiction, knockout of PPM1F in the dorsal raphe nucleus (DRN) 5-HT neurons enhances susceptibility to methamphetamine-induced conditioned place preference [4]. In cancer research, knockdown of PPM1F inhibits ovarian cancer tumor formation, as it regulates the phosphorylation of ITGB1 [6]. In endometrial cancer, BHLHE40 enhances AMPKα phosphorylation by suppressing PPM1F transcription, and their expressions correlate with patient prognosis [7].

In summary, Ppm1f is a key regulator in multiple biological processes. Gene knockout studies in mice have revealed its significance in embryonic development, mental diseases such as depression and anxiety, drug addiction, and cancer. These findings provide valuable insights into the biological functions of Ppm1f and potential therapeutic targets for related diseases.