ROCK2 (Rho-associated kinase 2) is a serine/threonine protein kinase that belongs to the Rho GTPase effector family and plays a crucial role in the regulation of the cytoskeleton dynamics, cell migration, proliferation, and survival. ROCK2 has been identified as a key driver in the development of various cancers. In acute myeloid leukemia (AML), increased expression of ROCK2 leads to lower rates of complete remission and poorer overall survival. Inhibition of ROCK2 can enhance the sensitivity of AML cell lines and primary AML samples to drugs and reduce the activity of downstream signaling pathways. ROCK2 is a key modulator in immune regulation and fibrosis and has become a therapeutic target for chronic graft-versus-host disease (cGVHD). ROCK2 plays a primary regulatory role in axonal degeneration, neuronal death, and axonal regeneration in the central nervous system (CNS). Downregulation of ROCK2 can inhibit apoptosis, reduce axonal degeneration, and promote neurite outgrowth.