INF2 (inverted formin 2) is an actin-regulating protein that severs actin filaments and promotes their polymerization and depolymerization 1. Functionally, INF2 localizes to the endoplasmic reticulum and perinuclear cytoplasm where it catalyzes linear actin filament formation 2. INF2 plays a critical role in mitochondrial fission by promoting actin polymerization at ER-mitochondrial contact sites, functioning upstream of the fission protein Drp1 to drive initial mitochondrial constriction 2. The protein also regulates oxidative stress responses; INF2 knockdown promotes cell survival during oxidative stress by reducing mitochondrial ROS and restoring mitochondrial membrane potential through HIF1 pathway modulation 3. INF2 activity is tightly regulated through its diaphanous inhibitory domain (DID), which can be disrupted by pathogenic mutations 1. Disease-associated INF2 mutations cause focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth disease through gain-of-function mechanisms rather than haploinsufficiency 4. Mutant INF2 exhibits excessive actin polymerization, leading to altered intracellular trafficking, abnormal mitochondrial dynamics, and transcriptional reprogramming that causes podocyte loss and axonal degeneration 1. At least 80 pathogenic DID variants have been identified 1. INF2 mutations have also been implicated in atypical hemolytic uremic syndrome pathogenesis 5. Pharmacological targeting of INF2 or actin polymerization represents a promising therapeutic strategy for INF2-linked diseases 1.