CARMIL3 (capping protein regulator and myosin 1 linker 3) is a multidomain cytoplasmic and membrane-associated protein that regulates actin dynamics through interaction with capping protein 1. It contains a conserved membrane-binding domain necessary for localization to cellular membranes and functions in cytoskeletal regulation 2. Primary functions include regulation of actin-based cell migration and lamellipodial assembly 1. CARMIL3 is critical for tumor metastasis, particularly metastatic colonization, through maintaining adherens junctions and E-cadherin transcription while protecting β-catenin from degradation 1. High CARMIL3 expression correlates with poor survival in breast and prostate cancer patients 1. Additionally, CARMIL3 regulates transcription of proinflammatory cytokines (IL-6, TNF-α, IL-1β, IL-23) in macrophages through NF-κB signaling, balancing inflammation and tissue homeostasis 3. In neuronal development, CARMIL3 localizes to nascent synapses where it facilitates capping protein recruitment and is required for synaptic spine maturation and AMPAR-mediated synapse unsilencing 4. Following ischemic stroke, CARMIL3 expression is upregulated specifically in neurons within ischemic regions, serving as a molecular signature associated with neuronal edema, impaired autophagy, and oxidative stress 5. These diverse functions establish CARMIL3 as a critical regulator of actin dynamics in cancer progression, immune response, neuronal development, and ischemic injury.