CARMIL2 (capping protein regulator and myosin 1 linker 2) is a cytosolic scaffold protein that serves dual critical functions in cellular motility and immune signaling. In cellular migration, CARMIL2 regulates actin polymerization by preventing capping protein activity at barbed ends of actin filaments, thereby promoting cell protrusion formation, lamellipodial assembly, and invadopodia formation during wound healing 1. The protein provides a molecular link between vimentin intermediate filaments and actin networks, with both vimentin localization and capping protein binding being essential for its cellular functions 1. In immune function, CARMIL2 is indispensable for CD28-mediated T cell costimulation, specifically enabling NF-κB but not AP-1 or NFAT activation through its interaction with the CARD11 adaptor protein 23. CARMIL2 deficiency causes a severe combined immunodeficiency (Immunodeficiency 58) characterized by recurrent infections, inflammatory bowel disease, EBV-related smooth muscle tumors, and reduced memory T cell, NK cell, and memory B cell populations 24. The protein also plays a crucial role in T cell metabolic reprogramming, with deficiency disrupting mTOR signaling, glycolysis, and glutamine metabolism 5. CARMIL2 mutations can present with pediatric inflammatory bowel disease even without overt immunodeficiency signs 6.