FMNL1 (formin-like 1) is a formin-family actin-regulatory protein located on chromosome 17 that exists as A and B isoforms through alternative splicing 1. It contains conserved FDD, FH1, and FH2 domains characteristic of formin proteins 1. Primary Function: FMNL1 regulates actin cytoskeleton dynamics and cell migration. It is essential for podosome formation and macrophage migration through complex extracellular matrices, with targeted suppression of FMNL1 decreasing macrophage migration similarly to inhibition of all expressed formins 2. In T cells, FMNL1 localizes to the cell rear and promotes nuclear deformation in confined environments, enabling efficient migration through diverse tissue environments 3. Mechanism: FMNL1 nucleates and regulates actin filament dynamics at adhesion structures and phagocytic sites. It specifically enriches at macrophage pseudopods during Borrelia coiling phagocytosis, with FMNL1 knockdown decreasing bacterial internalization 4. The protein can associate with the nucleus and functions distinctly from mDia1 in promoting migration 3. Disease Relevance: FMNL1 expression correlates with cancer aggressiveness. High FMNL1 expression in nasopharyngeal carcinoma promotes invadopodia formation, epithelial-mesenchymal transition, and invasiveness through MTA1 upregulation 5. In gastric cancer, elevated FMNL1 associates with larger tumor size and higher disease stage 6. FMNL1 is implicated in polarity control, invasion, migration, and metastasis through Rho-related signaling 1. Clinical Significance: A 5-gene signature including FMNL1-DT predicts immunotherapy response in non-small cell lung cancer, with high accuracy in stratifying responders 7. FMNL1 represents a potential therapeutic target to modulate macrophage-mediated inflammation or fine-tune T cell migration behavior 2.