NCKAP1L (NCK associated protein 1 like) is a hematopoietic-specific regulator of actin cytoskeleton dynamics that serves as a core component of the WAVE regulatory complex (WRC), which mediates branched actin polymerization 1. In immune cells, NCKAP1L controls lymphocyte development, activation, and proliferation, as well as neutrophil migration and phagocytosis 2. Within the WAVE2 complex, NCKAP1L restrains excessive T-cell degranulation while enabling efficient T-lymphocyte and neutrophil migration 2. The protein also regulates mTORC2-dependent AKT phosphorylation, supporting T-cell proliferation and cytokine secretion 3. In humans, recessive NCKAP1L mutations cause immunodeficiency 72 with autoinflammation and lymphoproliferation, characterized by combined immunodeficiency, lymphoproliferation, hyperinflammation with hemophagocytic features, and impaired T-cell immune synapse formation 2. Beyond immune function, NCKAP1L regulates actin dynamics in other contexts: HNF3α promotes renal fibrosis following ischemia-reperfusion injury by upregulating NCKAP1L expression 4, and NCKAP1L expression associates with improved osteosarcoma prognosis through immune cell recruitment 5. Emerging evidence suggests NCKAP1L as a diagnostic biomarker in sepsis and potentially other inflammatory conditions 6.