PPM1F (protein phosphatase, Mg2+/Mn2+ dependent 1F) is a serine/threonine phosphatase belonging to the metal-dependent PPM family that binds manganese/magnesium ions in its catalytic center 1. As a calmodulin-dependent protein kinase phosphatase, PPM1F dephosphorylates and deactivates CaMKII and CaMKIV upon their activation 2, regulating intracellular calcium signaling. PPM1F also controls integrin activity by selectively dephosphorylating a conserved threonine phospho-switch (T788/T789) in integrin β cytoplasmic domains, determining association with either integrin activators (talin/kindlin-2) or suppressors (filaminA) 3. Additionally, PPM1F regulates energy metabolism through dephosphorylation of AMPKα, with transcriptional regulation by BHLHE40 4. Clinically, PPM1F dysregulation is implicated in multiple diseases. PPM1F expression is stress-regulated and downregulated in blood of individuals with comorbid PTSD and depression, with genetic variants (rs17759843, rs9610608) associated with altered cortical thickness in prefrontal regions 56. In cancer, elevated PPM1F expression correlates with enhanced invasiveness and poor prognosis through integrin signaling 7, while smoking-induced upregulation promotes breast cancer by dephosphorylating p53 and BAX 8. PPM1F knockout is embryonic lethal at E10.5, indicating essential developmental roles 3.