Neurofibromatosis　type　1　(NF1)　is　an　autosomal　dominant　genetic　disorder　caused　by　mutations　of　the　NF1　gene,　which　is　characterized　by　multiple　café-au-lait　macules　and　neurofibromas.　There　are　still　no　standardized　treatment　strategies　for　NF1　internationally.　The　NF1　gene　is　large　and　encodes　neurofibromin　(NF)　that　participates　in　cell　proliferation.　The　disease　mechanism　is　complex,　which　presents　major　challenges　for　drug　development.　Various　signaling　pathways　including　the　RAF/MEK/ERK,　PI3K/AKT/mTOR,　WNT/β-catenin,　and　HIPPO/TAZ/YAP　pathways　have　been　studied　in　NF1.　MEK1/2　inhibitors　targeting　the　RAF/MEK/ERK　pathway,　such　as　selumetinib,　have　been　approved　for　the　treatment　of　NF1　and　inoperable　plexiform　neurofibromas　(PNF).　Recent　studies　highlighted　the　crucial　role　of　the　NF1　tumor　microenvironment,　comprising　Schwann　cells　(SCs)　and　their　precursors,　mast　cells,　macrophages,　T　cells,　dendritic　cells,　the　extracellular　matrix,　and　surrounding　blood　vessels,　in　NF1　pathogenesis.　Current　treatments　for　NF1　include　tumor　resection,　radiotherapy,　and　pharmacotherapy,　all　of　which　have　limitations.　There　is　an　urgent　need　for　exploration　of　novel　therapeutic　agents　targeting　NF1　signaling　pathways　and　the　tumor　microenvironment.　This　review　summarizes　the　current　research　progress　in　NF1-related　signaling　pathways　and　the　microenvironment　components.　It　specifically　highlights　the　changes　of　the　signaling　pathways　caused　by　NF1　gene　mutations　and　the　abnormal　tumor　microenvironment　components,　and　analyzes　the　possible　pathogenesis　of　NF1　to　provide　new　insights　for　early　diagnosis,　treatment,　prevention,　and　drug　development　in　clinical　NF1　management.　©　2024　Chinese　Society　of　Biochemistry　and　Molecular　Biology,　Peking　University.　All　rights　reserved.