RAS proteins are binary switches that cycle between active GTP-bound and inactive GDP-bound states, playing a crucial role in signal transduction. Mutations in RAS genes or their regulators can lead to persistent RAS activation, contributing to diseases such as cancer, RASopathies, and psychiatric disorders. RAS proteins interact with membranes, and their activity is regulated by GEFs and GAPs, which control the switch between GTP and GDP states. The structural basis of RAS function involves two switch regions, switch-I and switch-II, which undergo conformational changes during GTP binding and hydrolysis. RAS effectors, such as RAF kinases, PI3K, and RalGDS, are recruited to the plasma membrane to initiate signaling pathways. RAS proteins also interact with various effectors, and their activity is influenced by membrane lipid composition. RAS effectors can be diverse, but the fundamental mechanism of the binary switch is highly conserved. RAS proteins are localized to membranes through lipid modifications and interact with specific effectors. RAS mutations are common in cancer, with KRAS being the most frequently mutated RAS gene. RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, are caused by germline mutations that activate the RAS/MAPK pathway. These conditions are associated with a range of clinical features and can lead to various malignancies. RAS proteins also play a role in psychiatric and neurodevelopmental disorders, with mutations in genes such as SYNGAP1 contributing to intellectual disability and autism. Therapeutic approaches targeting RAS include inhibitors of GEFs and GAPs, as well as compounds that bind to RAS proteins. However, developing effective RAS inhibitors remains challenging due to the lack of a deep binding pocket in RAS proteins. Recent advances in fragment-based screening have identified promising compounds that bind to RAS and may offer new therapeutic strategies for RAS-driven diseases.RAS proteins are binary switches that cycle between active GTP-bound and inactive GDP-bound states, playing a crucial role in signal transduction. Mutations in RAS genes or their regulators can lead to persistent RAS activation, contributing to diseases such as cancer, RASopathies, and psychiatric disorders. RAS proteins interact with membranes, and their activity is regulated by GEFs and GAPs, which control the switch between GTP and GDP states. The structural basis of RAS function involves two switch regions, switch-I and switch-II, which undergo conformational changes during GTP binding and hydrolysis. RAS effectors, such as RAF kinases, PI3K, and RalGDS, are recruited to the plasma membrane to initiate signaling pathways. RAS proteins also interact with various effectors, and their activity is influenced by membrane lipid composition. RAS effectors can be diverse, but the fundamental mechanism of the binary switch is highly conserved. RAS proteins are localized to membranes through lipid modifications and interact with specific effectors. RAS mutations are common in cancer, with KRAS being the most frequently mutated RAS gene. RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, are caused by germline mutations that activate the RAS/MAPK pathway. These conditions are associated with a range of clinical features and can lead to various malignancies. RAS proteins also play a role in psychiatric and neurodevelopmental disorders, with mutations in genes such as SYNGAP1 contributing to intellectual disability and autism. Therapeutic approaches targeting RAS include inhibitors of GEFs and GAPs, as well as compounds that bind to RAS proteins. However, developing effective RAS inhibitors remains challenging due to the lack of a deep binding pocket in RAS proteins. Recent advances in fragment-based screening have identified promising compounds that bind to RAS and may offer new therapeutic strategies for RAS-driven diseases.