Rho-kinase (ROCK) is a serine/threonine kinase that belongs to the AGC family of kinases and acts as an effector of the small GTPase Rho. It plays a crucial role in regulating the cytoskeleton, cell polarity, and various cellular processes such as contraction, motility, and gene expression. ROCK is involved in a wide range of diseases, including vasospasm, pulmonary hypertension, nerve injury, and glaucoma, making it a potential therapeutic target. This review discusses the structure, function, and modes of activation and inhibition of ROCK. ROCK consists of an N-terminal catalytic domain, a central coiled-coil domain, and a C-terminal PH domain interrupted by a Cys-rich region. It is activated by Rho binding to its C-terminal portion and can also be activated by certain lipids such as arachidonic acid. ROCK has two main isoforms, ROCK1 and ROCK2, which have distinct expression patterns and functions. ROCK1 is involved in stress fiber formation, while ROCK2 is involved in phagocytosis and cell contraction. Both isoforms are expressed in various tissues, with higher levels in specific organs. ROCK functions by phosphorylating its substrates, including myosin light chain (MLC) phosphatase, which regulates MLC phosphorylation and thus affects cell contraction. ROCK also phosphorylates ERM proteins, which are involved in cell adhesion and cytoskeletal organization. ROCK is involved in cell migration, neurite elongation, and cytokinesis. It regulates the formation of actin stress fibers and focal adhesions, and is essential for cell polarity and directional migration. ROCK inhibitors, such as Fasudil and Y-27632, have been developed and used in various studies to investigate the physiological roles of ROCK. These inhibitors are ATP-competitive and have shown potential in the treatment of diseases such as glaucoma. ROCK is also involved in the regulation of cell survival and apoptosis, and its inhibition can have protective effects in certain conditions. In summary, ROCK is a key regulator of the cytoskeleton and cell polarity, involved in various cellular processes and pathologies. Its functions are regulated by multiple mechanisms, including the activation of Rho, phosphorylation of substrates, and interactions with other signaling molecules. Understanding the role of ROCK in different cellular processes is essential for developing targeted therapies for diseases associated with its dysregulation.Rho-kinase (ROCK) is a serine/threonine kinase that belongs to the AGC family of kinases and acts as an effector of the small GTPase Rho. It plays a crucial role in regulating the cytoskeleton, cell polarity, and various cellular processes such as contraction, motility, and gene expression. ROCK is involved in a wide range of diseases, including vasospasm, pulmonary hypertension, nerve injury, and glaucoma, making it a potential therapeutic target. This review discusses the structure, function, and modes of activation and inhibition of ROCK. ROCK consists of an N-terminal catalytic domain, a central coiled-coil domain, and a C-terminal PH domain interrupted by a Cys-rich region. It is activated by Rho binding to its C-terminal portion and can also be activated by certain lipids such as arachidonic acid. ROCK has two main isoforms, ROCK1 and ROCK2, which have distinct expression patterns and functions. ROCK1 is involved in stress fiber formation, while ROCK2 is involved in phagocytosis and cell contraction. Both isoforms are expressed in various tissues, with higher levels in specific organs. ROCK functions by phosphorylating its substrates, including myosin light chain (MLC) phosphatase, which regulates MLC phosphorylation and thus affects cell contraction. ROCK also phosphorylates ERM proteins, which are involved in cell adhesion and cytoskeletal organization. ROCK is involved in cell migration, neurite elongation, and cytokinesis. It regulates the formation of actin stress fibers and focal adhesions, and is essential for cell polarity and directional migration. ROCK inhibitors, such as Fasudil and Y-27632, have been developed and used in various studies to investigate the physiological roles of ROCK. These inhibitors are ATP-competitive and have shown potential in the treatment of diseases such as glaucoma. ROCK is also involved in the regulation of cell survival and apoptosis, and its inhibition can have protective effects in certain conditions. In summary, ROCK is a key regulator of the cytoskeleton and cell polarity, involved in various cellular processes and pathologies. Its functions are regulated by multiple mechanisms, including the activation of Rho, phosphorylation of substrates, and interactions with other signaling molecules. Understanding the role of ROCK in different cellular processes is essential for developing targeted therapies for diseases associated with its dysregulation.