PFN1 (profilin 1) is an actin-binding protein with multifaceted cellular roles beyond its well-characterized cytoskeletal functions. As an actin-sequestering protein, PFN1 modulates actin polymerization in a concentration-dependent manner and binds phosphatidylinositol-4,5-bisphosphate (PIP2) 1. Recently, PFN1 has emerged as a critical regulator in vascular smooth muscle cell (VSMC) phenotype switching and neointimal hyperplasia, where its protein levels are controlled by N6-methyladenosine modification via METTL3-YTHDF3 pathways, promoting VSMC dysfunction through the p-ANXA2/STAT3 signaling axis 1. In the nervous system, PFN1 mutations cause amyotrophic lateral sclerosis (ALS) with characteristic lower limb onset around age 50 and absence of cognitive impairment 2. Pathogenic ALS-PFN1 variants impair microglial vesicular degradation and phagocytosis through enhanced PI3P binding, suggesting gain-of-toxic function in autophagic pathways 3. Beyond neurodegeneration, PFN1 polymorphisms associate with bone mineral density and osteoporotic fracture risk in males 4, while increased PFN1 expression suppresses psoriatic inflammation by inhibiting IκBζ signaling 5. In hepatic encephalopathy, PFN1 downregulation contributes to astrocytic dysfunction and neurological decline 6. Notably, perforin (PFN, distinct from PFN1) mutations cause hemophagocytic lymphohistiocytosis and immune dysregulation 7.